Chapter 3 Vocab Flashcards
The Chemistry of Behavior
a substance produced inside the body
Endogenous
Chapter 3 (p82-83)
substances arising from outside the body
Exogenous
Chapter 3 (p82-83)
referring to the “transmitting” side of a synapse
Presynaptic
Chapter 3.1 (p84-85)
cellular location at which information is transmitted from a neuron to another cell
Synapse
Chapter 3.1 (p84-85)
a specialized protein that is imbedded in the cell membrane, allowing it to selectively sense and react to molecules of a corresponding neurotransmitter or drug
Neurotransmitter
Chapter 3.1 (p84-85)
a specialized protein that is embedded in the cell membrane, allowing it to selectively sense and react to molecules of a corresponding neurotransmitter or drug
Neurotransmitter receptors
Chapter 3.1 (p84-85)
referring to the region of a synapse that receives and responds to neurotransmitter
Postsynaptic
Chapter 3.1 (p84-85)
process by which vesicles release their cargo of molecules of neurotransmitter into the synaptic cleft
Exocytosis
Chapter 3.1 (p84-85)
reabosorption of molecules of neurotransmitter by the neurons that released them, thereby ending the signaling activity of the transmitter molecules
Reuptake
Chapter 3.1 (p84-85)
a specialized membrane component that returns transmitter molecules to the presynaptic neuron for reuse
transporters
Chapter 3.1 (p84-85)
a receptor protein containing an ion channel that opens when the receptor is bound by an agonist
Ionotropic Receptor (also called a ligand-gated ion channel)
Chapter 3.1 (p85-86)
a type of synapse that, when active, causes a local depolarization that increases the likelihood the neuron will fire an action potential
Excitatory Synapse
Chapter 3.1 (p85-86)
a type of synapse that, when active, causes a local hyperpolarization that decreases the likelihood the neuron will fire an action potential
Inhibitory Synapse
Chapter 3.1 (p85-86)
receptor protein that does not contain ion channels but may, when activated, use a second-messenger system to open nearby ion channels or to produce other cellular effects
metabotropic receptors
(involves G proteins and second messengers)
Chapter 3.1 (p86)
any type of receptor having functional characteristics that distinguish it from other types of receptors of the same neurotransmitter
receptor subtypes
Note: there are at least 15 different subtypes of serotonin receptors
Chapter 3.1 (p86)
a type of receptor that, when activated extracellularly, initiates a G protein signaling mechanism inside the cell
G protein-coupled receptors (GPCRs)
Chapter 3.1 (p86)
first neurotransmitter to be discovered
Acetylcholine
Chapter 3.1 (p87)
- frog heart experiment to determine whether transmission of message was electrical or chemical (soups v sparks)
- vagus nerve uses a chemical neurotransmitter, not a direct electrical connection, to communicate to cells of the heart and cause it to slow down (chemical neurotransmission)
- discoverer of the 1st neurotransmitter
Otto Loewi
Chapter 3.1 (p87)
List the qualifications a substance must meet to be considered a neurotransmitter.
5
- it can be synthesized by presynaptic neurons and stored in axon terminals
- it is released when action potentials reach the terminals
- it is recognized by specific receptors located on the postsynaptic membrane
- is causes changes in the postsynaptic cell
- blocking its release interferes with the ability of the presynaptic cell to affect the postsynaptic cell
3.2 (pH15)
A neurotransmitter that is an amino acid.
Examples: GABA, glycine, and glutamate
a neurotransmitter family/subfamily type
Amino acid neurotransmitters
Compare to: amine NTs, gas NTs, and peptide NTs
3.2(p.H15-89)
a neurotransmitter consisting of a short chain of amino acids
Examples: oxytocin, Beta-endorphin, vasopressin
a neurotransmitter family/subfamily type
Peptide neurotransmitters (also called neuropeptides)
Compare to: amine NTs, amino acid NTs, gas NTs
3.2(p.H15-89)
short chains of amino acids
Peptides
3.2(pH15-89)
a neurotransmitter based on modifications of a single amino acid nucleus
Examples: acetylcholine, serotonin, dopamine
a neurotransmitter family/subfamily type
Amine neurotransmitters
Compare to: amino acid NTs, gas NTs, peptide NTs
3.2(p.H15-89)
a neurotransmitter that is a soluble gas. They usually act, in a retrograde fashion, on presynaptic neurons.
Examples: nitric oxide, carbon monoxide
a neurotransmitter family/subfamily type
Gas neurotransmitters
3.2(p.H15-89)
an amino acid transmitter, the most common excitatory transmitter
Glutamate
3.2(p.H15-90)
a widely distributed amino acid transmitter, the main inhibitory transmitter in the mammalian nervous system
Gamma-aminobutyric acid (GABA)
3.2(p.H15-90)
Drugs called benzodiazepines potentially activate receptors for which neurotransmitter?
receptor subtype
GABA-A
3.2(p.H15-90)
synthesis and release of more than one type of neurotransmitter by a given presynaptic neuron
(neurotransmitter) co-localization
3.2(p.H15-90)
Name four classic neurotransmitters for moderating brain activity:
Acetylcholine, Dopamine, Serotonin, Norepinepherine
Note: Acetylcholine and amine transmitters have been tied to patterns of behavior and pathology, so these transmitter systems are major targets for drug development.
3.2(p90)
Basal forebrain to cortex, amygdala, and hippocampus
a neurotransmitter system/pathway
Cholinergic System
3.2(p90)
Includes two main pathways:
- Mesolimbocortical pathway: ventral tegmental area (VTA) to nucleus accumbens and cortex
- Mesostriatal pathway: substantia nigra to basal ganglia
a neurotransmitter system/pathway
Dopaminergic System
3.2(p90)
Includes pathways:
- locus coeruleus to forebrain
- lateral tegmental area to brainstem and spinal cord
a neurotransmitter system/pathway
Noradrenergic System
3.2(p90)
Midbrain raphe nuclei to forebrain; brainstem raphe nuclei to spinal cord
a neurotransmitter system/pathway
Serotonergic System
3.2(p90)
Dopaminergic pathway that projects to various locations in limbic system and cortex.
ventral tegmental area (VTA) to nucleus accumbens and cortex
Especially important for processing reward and likely where feelings of pleasure arise. Important for learning, shaped by positive reinforcement.
Abnormalities in this pathway are associated with some symptoms of schizophrenia
Mesolimbocortical system
in Dopaminergic system
3.2(p90)
Dopaminergic pathway that originates in midbrain (mesencephalin) around substantia nigra and projects axons to basal ganglia (striatum).
Only hundreds of 1000s of neurons in this system (but single axon can supply many synapses)
Plays crucial role in motor control.
When people lose many neurons in this pathway, they develop profound movement problems of Parkinson’s disease, including tremors.
A pathway in the dopaminergic system
Mesostriatal pathway
in Dopaminergic system
3.2(p90)
List the receptor subtypes and functions for:
Glutamate
Transmitters & Receptor Subtypes
Function(s):
- most abundant of all NTs and most important excitatory transmitter
- This NT’s receptors are crucial for excitatory signals
- NMDA receptors implicated in learning and memory
Known Receptor Subtypes:
- AMPA (ionotropic)
- Kainate (ionotropic)
- NMDA (ionotropic)
- mGluRs (metabotropic)
receptor subtype mGLuRs = metabotropic glutamate receptors
3.2(p.90-91) - Table 3.2
List the receptor subtypes and functions for:
Gamma-aminobutyric acid (GABA)
Transmitters & Receptor Subtypes
GABA receptors mediate most of brain’s inhibitory activity, balancing excitatory actions of glutamate.
Receptor subtypes:
- GABA-A (ionotropic): inhibitory in many brain regions, reducing excitability and preventing seizure activity
- GABA-B (metabotropic): also inhibitory, but by a different mechanism
3.2(p.90-91) - Table 3.2
List the receptor subtypes and functions for:
Acetylcholine (ACh)
Transmitters & Receptor Subtypes
Both types of ACh receptors are involved in cholinergic transmission in the cortex.
Receptor subtypes:
- muscarinic receptors (metabotropic)
- nicotine receptors (ionotropic): crucial for muscle contraction
3.2(p.90-91) - Table 3.2
List the receptor subtypes and functions for:
Norepinephrine (NE)
Transmitters & Receptor Subtypes
NE has multiple effects in visceral organs, important in sympathetic nervous system and fight-or-flight responses. In the brain, NE transmission provides an alerting and arousing function.
Receptor subtypes:
- a1, a2, B1, B2, and B3 receptors (all metabotrophic)
not actually “a” and “b.” a refers to alpha and b refers to beta.
3.2(p.90-91) - Table 3.2
List the receptor subtypes and functions for:
Dopamine (DA)
Transmitters & Receptor Subtypes
Functions: DA receptors are found throughout the forebrain. They are involved in complex behaviors, including motor function, reward, and higher cognition.
Receptor subtypes:
- D1 through D5 receptors (all metabotropic)
3.2(p.90-91) - Table 3.2
List the receptor subtypes and functions for:
Serotonin
Transmitters & Receptor Subtypes
Receptor subtypes/functions:
- 5-HT1 receptor family: has 5 members; different subtypes differ in distribution throughout brain
- 5-HT2 receptor family: has 3 members; may be involved in mood, sleep, and higher cognition
- 5-HT3 through 5-HT7 receptors: 5-HT3 receptors are particularly involved in nausea
All serotonin receptors except for 5-HT3 are metabotropic
3.2(p.90-91) - Table 3.2
List the receptor subtypes and functions for:
Miscellaneous Peptides
Transmitters & Receptor Subtypes
There are many specific receptors for peptides such as:
- opiates (delta, kappa, and mu receptors)
- cholecystokinin (CCK)
- neurotensin
- neuropeptide Y (NPY)
- and dozens more (all metabotropic)
Peptide transmitters have many different functions dependent on their anatomical localization. Some important examples include the control of feeding, sexual behaviors, and social functions.
3.2(p.90-91) - Table 3.2
Referring to cells that use acetylcholine as their synaptic transmitter.
Widespread loss of these neurons is associated with Alzheimer’s; in rats, disruption of these pathways interferes with learning and memory.
Plays a major role in neurotransmission in forebrain.
cholinergic
3.2(p.91-92)
A region, ventral to the basal ganglia, that is the major source of cholinergic projections in the brain and has been implicated in sleep.
basal forebrain
3.2(p.91-92)
A monoamine transmitter found in the midbrain–especially the substantia nigra–and it the basal forebrain.
dopamine (DA)
Note: only ~1mil of brain’s 80 billion neurons synthesize DA
3.2(p.91-92)
referring to cells that use dopamine as their synaptic transmitter
dopaminergic
3.2(p.91-92)
a brainstem structure that innervates the basal ganglia and is a major source of dopaminergic projections
substantia nigra
3.2(p.91-92)
a portion of the midbrain that projects dopaminergic fibers to the nucleus accumbens
ventral tegmental area (VTA)
3.2(p.91-92)
referring to cells that use serotonin as their synaptic neurotransmitter
this type of neuron is scarce in the brain (only about 200,000)
serotonergic
3.2(p92)
a string of nuclei in the midline of the midbrain and brainstem that contain most of the serotonergic neurons of the brain
raphe nuclei
raphe is Latin for “seam”
3.2(p92)
A synaptic transmitter that is produced in the raphe nuclei and is active in structures throughout the cerebral hemispheres.
Serotonin
AKA 5-HT
3.2(p92)
A synaptic transmitter that is produced in the raphe nuclei and is active in structures throughout the cerebral hemispheres.
Participate in several functions, including mood, vision, sexual behavior, anxiety, sleep, and many other functions.
5-HT
Short for its chemical name, 5-hydroxytryptamine; AKA serotonin
3.2(p92)
referring to cells using norepinephrine (noradrenaline) as a neurotransmitter
noradrenergic
3.2(p92)
A neurotransmitter active in both the brain and sympathetic nervous system. Participate in control of behaviors ranging from alertness to mood to sexual behavor (and more).
also known as noradrenaline
norepinepherine (NE)
3.2(p92)
a small nucleus in the brainstem whose neurons produce norepinephrine and modulate large areas of the forebrain
Hint: also known as “the blue spot”
locus coeruleus
compare: substantia nigra
3.2(p92)
a region of the brainstem that provides some of the norepinephrine-containing projections of the brain
lateral tegmental area
3.2(p92)
a type of endogenous peptide that mimics the effects of morphine in binding to opioid receptors and producing marked analgesia and reward
opioid peptides
Examples include: met-enkephalin, leu-enkephalin, beta-endorphin, dynorphin
3.2(p92)
A neurotransmitter that is released by the postsynaptic neuron, diffuses back acorss the synapse, and alters the functioning of presynaptic neuron. (Gas NTs can function as these).
Process may be crucial in memory formation and also functions like hair growth and penile erections.
retrograde transmitters
3.2(p93)
How are gas neurotransmitters different from traditional neurotransmitters?
3 ways
- produced in cellular locations other than the axon terminal, especially in the dendrites, and are not held in vesicles; the substance simply diffuses out of the neuron as it is produced
- no receptors in the membrane of the target cell are involved. Instead, gas transmitter diffuses into target cell to trigger the second messengers inside
- gas NTs can function as retrograde transmitters
3.2(p93)
one common meaning is “medicine used in the treatment of a disease”
Drug
3.3(p94)
compounds that alter brain function and thereby affect conscious experiences
Psychoactive drugs
3.3(p94)
psychoactive drugs that are used recreationally, with varying degrees of risk to the useer are soemtimes called:
Drugs of Abuse
3.3(p94)
ligand
3.3(p94)
agonists
3.3(p94)
receptor agonist
3.3(p94)
antagonist
3.3(p94)
receptor antagonist
3.3(p94)
blockers
3.3(p94)
partial agonists
3.3(p94)
referring to a substance, usually a drug, that is present in the body in a form that is able to interact with physiological mechanisms
free to act on the tartet tissue, and thus not in use elsewhere or in the process of being eliminated
bioavailability
3.3(p95)
biotransformation
3.3(p95)
pharmacokinetics
3.3(p95)
binding affinity
AKA affinity
3.3(p95)
efficacy
3.3(p95-96)
dose-response curve (DRC)
3.3(p95-96)
effective dose 50% (ED50)
3.3(p96) Figure 3.6 DRC
potency
3.3(p96) Figure 3.6 DRC
therapeutic index
3.3(p96) Figure 3.6 DRC
toxic dose 50% (TD50)
3.3(p96) Figure 3.6 DRC
lethal dose 50% (LD50)
3.3(p96) Figure 3.6 DRC
blood-brain barrier
3.3(p96)
Give examples, mechanisms, speed of effects for route of administration.
Ingestion
Forms: tablets, capsules, infusions/teas, suppositories
Examples: Many types of drugs/remedies can be ingested.
Details: Ingestion depends on absorption by the gut, which is somewhat slower than other routs and affected by digestive factors like stomach acidity and whether person has eaten.
Speed of effects: slow to moderate
3.3(p96) - Table 3.3 Routes of Administration
Give examples, mechanisms, speed of effects for route of administration.
Inhalation
Forms: smoking; nasal absorption (snorting); inhaled gases, powders, sprays
Examples: nicotine, cocaine, airplane glue and gas (and other organic solvents), various prescription drugs and hormone treatments
Details: inhalation methods take advantage of the rich vascularization of the nose and lungs to convey drugs directly into blood stream
Speed of effects: moderate to fast
3.3(p96) - Table 3.3 Routes of Administration
Give examples, mechanisms, speed of effects for route of administration.
Central Injection
Forms:
- intracerebroventricular (into ventricular system)
- intrathecal (into the cerebrospinal fluid of the spine)
- epidural (under the dura mater)
- intracerebral (directly into a brian region)
Examples: morphine for cancer pain (intrathecal); corticosteroid - local anesthetics for pain (epidural)
Details: central methods involve injection directly into the central nervous system and are used in order to circumvent blood-brain barrier, to rule out peripheral effects, or to directly affect discrete brain location.
Speed of effects: fast to very fast
3.3(p96) - Table 3.3 Routes of Administration
Give examples, mechanisms, speed of effects for route of administration.
Peripheral Injection
Forms: subcutaneous, intramuscular, intraperitoneal (abdominal), intravenous
Examples: many drugs
Details:
- subcutaneous (under the skin) injections tend to have slowest effects because they may difuse into nearby tissue in order to reach bloodstream
- intravenous injections have rapid effects because drug is placed directly into circulation
Speed of effects: moderate to fast
3.3(p96) - Table 3.3 Routes of Administration
condition, in which, with repeated exposure to a drug, and invididual becomes less responsive to a constant dose
(drug’s effectiveness diminishes with repeated treatments)
Drug tolerance
Or just “tolerance”
3.3(p96-97)
The form of drug tolerance that arises when repeated exposure to the drug causes the metabolic machinery of the body to become more efficient at clearing the drug.
Metabolic tolerance
Compare to functional tolerance
3.3(p96-97)
the form of drug tolerance that arises when repeated exposure to the drug causes receptors to be up-regulated or down-regulated
Functional tolerance
Compare to metabolic tolerance
3.3(p96-97)
A compensatory decrease in receptor availability at the synapses of a neuron.
Example: after repeated doses of an agonist drug, neurons by decrease number of receptors available to drug, thereby becoming less sensitive and countering the drug’s effect.
down-regulate
3.3(p96-97)
a compensatory increase in receptor availability at the synapses of a neuron
Ex. repeated doses of an antagonist drug might cuase an increase in number of receptors to become more sensitive and counteract the drug effect
up-regulate
3.3(p96-97)
What is a key feature of synapses that is crucial for neurotransmission and plasticity?
Hint: involved in developing drug tolerance
continual modification of receptor densities
See up-regulation and down-regulation.
3.3(p96-98)
a condition in which the development of tolerance for one drug causes an individual to develop tolerance for another drug
Example: people who have developed a tolerance to heroin tend to exhibit a degree of tolerance to all other drugs in opiate category (codeine, morphine, methadone, etc.) because all these drugs act on the same family of receptors.
cross-tolerance
3.3(p96-98)
Main categories of most common presynaptic drug effects:
3 categories
Effects on Transmitter…
- production
- release
- clearance
3.4(pH17)
3 ways presynaptic drugs can impact transmitter production
- Inhibition of transmitter synthesis
- Blockade of axonal transport
- Interference with storage of transmitters
3.4(pH17) - Figure 3.7
4 ways presynaptic drugs can impact transmitter release
- prevention of synaptic transmission
- Alteration of synaptic transmitter release trhough ca2+ (calcium) channel blockade
- alteration of transmitter release through modulation of presynaptic activity
- Alteration of synaptic transmitter release through other mechanisms
3.4(pH17) - Figure 3.7
4 ways presynaptic drugs can impact transmitter clearance
- Inactivation of transmitter reuptake
- Blockade of transmitter degredation
3.4(pH17) - Figure 3.7
drugs that block the calcium influx that normally drives release of transmitter into the synapse (interferes with presynaptic cell’s release of neurotransmitter)
calcium channel blocker
3.4(pH17-99)
receptor for synaptic transmitter that is located in the presynaptic membrane and tells the axon terminal how much transmitter has been released (kind of a feedback system for the cell)
drugs that stimulate these receptors can provide a false feedback signal, prompting the presynaptic cell to release less transmitter
Example: caffeine blocks an autoreceptor called the adenosine receptor
autoreceptors
3.4(p99-100)
a compound found in coffee and other plants that exerts a stimulant action by blocking adenosine receptors
by blocking adenosine receptors, caffeine increases the amount of neurotransmitter release, resulting in enhanced alertness
caffeine
3.4(p99-100)
something that potentiates or inhibits transmission of nerve impulse but not the actual means of transportation itself
Ex. Adenosine
neuromodulator
3.4(p99-100)
psychiatric drugs that work by blocking the presynaptic system that normally reabsorbs transmitter molecules after their release; this blocking action allows NTs to stay in the synaptic cleft a little longer and, therefore, have a greater impact on postsynaptic cell
reuptake inhibitors
3.4(p99-100)
Main categories of most common postsynaptic drug effects:
- direct effects on neurotransmitter receptors
- effects on cellular processes within postsynaptic neuron
3.4(p100-101) - Figure 3.8
Two ways postsynaptic drugs can effect transmitter receptors:
- Blockade of receptors
- Activation of receptors
3.4(p100-101) - Figure 3.8
Two ways postsynaptic drugs can effect cellular processes:
- Alteration of the number of postsynaptic receptors
- Modulation of second messengers
3.4(p100-101) - Figure 3.8
What do selective receptor agonists do?
bind to specific receptors and activate them, mimicking the natural NT at those receptors
ex. LSD stimulates subtype of serotonin receptors (5-HT2A receptors) found in visual cortex - this produces bizarre visual experiences
3.4(p101)
drugs to selectively activate, alter, or block targeted genes within DNA of neurons have ——— effects that could produce profound long-term changes in structure and function of neurons;
future research will likely focus on development of these types of drugs
genomic
3.4(p101)
an antischizophrenic drug that shows antagonist activity at dopamine D2 receptors
good at relieving positive symptoms of schizophrenia
first-generation antipsychotics
examples: Thorazine, Haldol, Loxitane
AKA neuroleptics or typical antipsychotics
3.5(pH18-102)
an antipsychotic drug with primary actions other than or in addition to the dopamine D2 receptor antagonism that characterizes earlier antipsychotics
second-generation antipsychotics
AKA atypical antipsychotic or atypical neuroleptic
3.5(pH18-102)
emergent symptoms and behaviors that were previously absent (e.g. hallucinations and delusions)
positive symptoms of schizophrenia
3.5(pH18-102)
symptoms that involve impairment or loss of a behavior (e.g., social withdrawal, blunted emotional responses)
negative symptoms of schizophrenia
3.5(pH18-102)
psychiatric disorders marked by emotional disruptions (e.g., depression and/or mania)
affective disorders
3.5(p102)
drug that relieves symptoms of depression by increasing synaptic transmission.
name 3 categories
antidepressant
3 major categories:
- monoamine oxidase inhibitors
- trycyclics
- selective serotonin reuptake inhibitors
3.5(p102)
enzyme that breaks down monoamine neurotransmitters, thereby inactivating them
blocks enzyme responsible for breaking down NTs like dopamine, serotonin, and norepinephrine, allowing them to accumulate in synapses leading to improvement in mood
monoamine oxidase (MAO) inhibitors
3.5(p102)
antidepressant that acts by increasing the synaptic accumulation of serotonin and norepinephrine
promote accumulation of NTs in synapse by blocking reuptake of transmitter molecules into the presynaptic terminal
tricyclic antidepressants
3.5(p102)
a drug, used to treat depression and anxiety, that blocks the reuptake of transmitter at serotenergic synapses
examples: Prozak, Celexa
selective serotonin reuptake inhibitors (SSRIs)
3.5(p102)
any of a class of drugs that promote the synaptic accumulation of serotonin and norepinephrine by blocking transmitter reuptake
serotonin-norepinephrine reuptake inhibitors (SNRIs)
3.5(p102)
a drug that reduces the excitability of neurons
have a strong potential for intoxication and addition
Examples: Alcohol, opium
depressants
3.5(p102)
an early anxiolytic and sleep aid that has depressant activity in the nervous system; addictive and easy to overdose on; also used to avoid epileptic seizures
Example: phenobarbital
barbiturate drugs
3.5(p102)
substance that is used to reduce anxiety
Examples: alchohol, opiates, barbiturates, benzodiazepines
anxiolytics
i.e., antianxiety drugs
3.5(p102)
any class of antianxiety drugs that are noncompetitive agonists of GABAA receptors in the CNS
(enhance GABA effects, because GABA is inhibitory, benzos help GAPA to produce larger inhibitory postsynaptic potentials than it would produce alone. The net effect is a reduction in neuron excitability)
benzodiazepines
Example: Valium, Xanax, Ativan
3.5(p102)
extracted from poppies
drugs based on ——— are potent painkillers
opium
Papaver somniferum
3.5(p.103)
opiate compound derived from poppy flower
very effective analgesic
morphine
3.5(p.103)
an absense of or reduction in pain
analgesic
i.e., painkiller
3.5(p.103)
diacetylmorphine, an artifically modified, very potent form of morphine
heroin
3.5(p.103)
a receptor that responds to endogenous opioids and/or exogenous opioids (including morphine, heroin, and codeine)
opioid receptors
3.5(p103-104)
an area in the midbrain with high density of opioid receptors and, as result, is an area where opiates exert painkilling effects
periaqueductal gray
3.5(p103-104)
studies in which radioactive forms of drugs are used to highlight regions showing highest density of receptor binding (warmer colors = more binding)
Findings: drugs belonging to opioid, cannabinoid, and cocaine categories vary in their binding patterns but some brain regions are affected by almost all such substances
radioligand binding studies
3.5(p104) Figure 3.10
Per findings from radioligand binding studies, why might opioid, cannabinoid, and cocaine elicit pleasurable experiences?
Many drugs affect cortical sites and almost all will activate mesolimbocortical DA (dopamine) pathway, terminating in basal ganglia
3.5(p104) Figure 3.10
any class of opium-like peptide transmitters that have been referred to as the body’s own narcotics
endogenous opioids
3 kinds: enkephalins, endorphins, dynorphins
3.5(p.104)
Name 3 major families of endogenous opioids:
- enkephalins (from the Greek en, “in,” and kephale, “head”)
- endorphins (a contraction of endogenous morphine)
- dynorphins (short for dynamic endorphins, in recognition of their potency and speed of action)
3.5(p.104)
Name 3 kinds of opioid receptors:
delta, kappa, and mu (all of which are metabotropic)
3.5(p.104)
How does Narcan work to rescue people from overdose?
it blocks opioid receptors, which rapidly reverses effects of overdose
3.5(p.104)
plant derivation has been used for thousands of years and is typically administered by smoking, vaping, or eating edible products
usually produces pleasant relaxation and mood alteration, though it can occasionally cause stimulation and paranoia
Drugs & Related Stuff
Cannabis
3.6(p.H19-105)
The major active ingredient in cannabis, thought to produce the “high” feeling that the drug is known for
Drugs & Related Stuff
delta-9-tetrahydrocannabinol (THC)
3.6(p.H19-105)
One of the two major types of active compounds in cannabis, which appears to have anxiolytic effects as well as other medicinal actions
Drugs & Related Stuff
Cannabidiol (CBD)
Drugs
3.6(p.H19-105)
receptor that responds to endogenous and/or exogenous cannabinoids
cannabinoid receptors
3.6(p105-106)
Found in: substantia nigra, hippocampus, cerebellar cortex and cerebral cortex
Cannabinoid receptors
3.6(p105-106)
an endogenous ligand of cannabinoid receptors, thus an analog of cannabis that is produced by the brain
Endocannabinoids
Drugs
3.6(p105-106)
an endogenous substance that binds to the cannabinoid receptor molecule
produces some of the most familiar physio and psychological effects of cannabis use, such as mood improvement, pain relief, lower blood pressure, nausea relief, improvements in glaucoma, etc.
Anandamide
from the Sanskrit ananda, meaning “bliss”
3.6(p105-106)
drug that enhances the excitability of neurons, typically producing an overall alerting, activating effect
stimulant
drugs; compare: depressant
3.6(p105-106)
Name some examples of stimulants:
nicotine, caffeine, cocaine, amphetamines
drugs
3.6(p105-106)
a compound found in plants, including tobacco, that stimulates nicotinic acetylcholine receptors
nicotine
drugs
3.6(p105-106)
Why does smoking/vaping cigs or ecigs have a more rapid effect than nicotine from other tobacco products?
it is directly delivered to the large surface of the lungs and, as result, enters the blood and brain more rapidly
3.6(p105-106)
What are some short and long-term impacts of nicotine use?
Short-term:
- increases heart rate
- increases blood pressure, increases digestive action
- increases alertness
- in all, these effects make tobacco use pleasurable
Long-term:
- impacts on physiological development
and cognitive development
- tar on lungs = lung cancer, emphysemia
- addictive
Drugs
3.6(p105-106)
How might nicotine impact development?
due to changes in pubertal development of cholinergic and glutamaterigic systems and, possibly, long-lasting modifications of neural function
Drugs
3.6(p106)
How does nicotine exert its effects in the body?
through nicotinic ACh receptors, which are found in high concentrations in the brain, including the cortex – this is one way that nicotine enhances some aspects of cognitive performance
nicotinic receptors also:
- are acted upon by nicotine in ventral tegmental area to exert rewarding/addicting effects
- drive contraction of skeletal muscles
- drive activation of various visceral organs
Drugs
3.6(p106)
a drug of abuse, derived from the coca plant, that acts by enhancing catecholamine neurotransmission
cocaine
Drugs
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How does cocaine exert its stimulant effects?
blocks the reuptake of monoamine transmitters (especially dopamine and norepinephrine), causing transmitters to accumulate in synapses throughout much of the brain, therefore boosting their effects
Drugs
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List short-term and long-term impacts of cocaine use:
Short-term:
- powerful and pleasant stimulant effects
Long-term:
- highly addictive with high rates of relapse
- potential for stroke
- potential for psychosis
- loss of gray matter in frontal lobes
- severe mood disturbances
- in combination with other substances, runs the risk of dual dependence (ex. cocaine metabolized in presense of alcohol yields an active cocaethylne, to which user may develop addtl addiction)
-
Drugs
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What is cocaethylne?
An active metabolite yielded when cocaine is metabolized in the presence of alcohol; puts cocaine users at risks of developing another addiction/dual dependence
Drugs
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molecule that resembles structure of the catecholamine transmitters and enhances their activity
(induces accumulation of DA and norepinephrine in synapse)
amphetamine
Drugs; aka “speed”
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How does amphetamine work differently than cocaine?
- amphetamine acts within axon terminals to cause larger-than normal release of NT when the synapse is activated
- amphetamine then interferes with clearance of released transmitter by blocking reuptake and metabolic breakdown
The result is the affected synapses become unnaturally potent with strong impacts on behavior.
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List short- and long-term impacts of amphetamine use:
Short-term:
- increased vigor and stamina
- wakefulness
- decreased appetite
- euphoria
Resistance/tolerance, requiring larger doses leading to symptoms like:
- sleeplessness
- severe weight loss
- general deterioration of mental/physical condition
Long-term, may lead to symptoms similar to schizophrenia:
- compulsivity
- agitated behavior
- irrational suspiciousness
- neglect of diet/basic hygeine
- peripheral effects like high blood pressure, tremor, dizziness, sweating, rapid breathing, nausea
- brain damage (long after use of meth)
-
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African shrub that, when chewed, acts as a stimulant
khat
or qat; Drugs
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amphetamine-like stimulants released when khat is chewed
many types of synthetic ——, known collectively as “bath salts,” have been developed and marketed in recent years
these new designer drugs, especially mephedrone (plant food or “meow meow”) are rapidly growing in popularity despite potential for damaging effects on brain, muscular system, and kidneys
cathinones
Drugs
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How does alcohol work?
has a biphasic effect on nervous system: at first, acts as a stimulant, then it has a more prolonged depressant phase (disinhibition in neural activity NOT depression as in the mental health condition)
biphasic nature is thought to be result of alcohol’s effects on several different NT systems, like glutamate and GABA
inhibits neural excitability in multiple brain regions via an action on GABA receptors, resulting in the social disinhibition, poor motor control and sensory disturbances that we call drunkenness
additionally, alcohol activates dopamine-mediated reward symptoms of the brain, accounting for some of the pleasure associated with drinking
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a family of developmental disorders that vary in severity, resulting from fetal exposure to alcohol consumed by the mother
severe cases, associated with levels of alcohol abuse by the mother, include intellectual disability and facil abnormalities
Figure 3.11 - MRI of healthy infant brain vs. infant w FASD
- FASD MRI - reduced gray matter, complete absense of corpus callosum, abnormal organization of the brain; characteristic deformities of head and face
fetal alcohol spectrum disorder (FASD)
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Are the impacts of alcoholism on the brain permanent?
Probably not – after just 1 week of abstinence, average volume of multiple brain regions noticeably increased in group of alcoholics copared with alcoholic and nonalcoholic control groups.
Not clear how much cognitive improvements accompany these changes, but results illustrate potential benefits of reduced intake in heavy drinkers
3.6(p109) - Figure 3.12
a drug that alters sensory perception and produces peculiar experiences; the various ———– are diverse in their neural actions
hallucinogens
aka psychadelics or entheogens
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Explain why the term “hallucinogens” is a misnomer.
a hallucination is a novel perception that takes place in the absense of sensory stimulation (hearing voices, seeing something that isn’t there), BUT drugs in this category mostly alter or distort existing perceptions (mainly visual in nature)
Users may see fantastic images, but they are usually aware that these altered perceptions are not real events.
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a hallucinogenic drug that structurally resembles serotonin and strongly activates 5-HT2A receptors found in especially heavy concentrations in the visual cortex
LSD
aka lysergic acid diethylamide or “acid”; drug
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a hallucinogen that is unusual among other hallucinogens in that it acts on the opioid kappa receptor
Salvia divinorum
Drugs
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the Father of LSD
accidentally discovered LSD by taking it in 1943, and devoted the rest of his career to studying it.
Albert Hofmann
People & Theories category
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a drug that is widespread in use in medical settings as a component of anesthesia, but also has significant hallucinogenic properties
Acts principally (but not exclusively) to block NMDA receptors, ——– increases activity in prefrontal cortex and hippocampus, producing feelings of depersonalization and detachment from reality.
Low doses have potent/rapid antidepressant effect that may help ease symptoms in resistant cases.
Ketamine
Drugs
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a drug of abuse that stimulates visual cortical 5-HT2A receptors while also changing levels of dopamine and certain hormones (e.g., prolactin, oxytocin) that have been associated with prosocial feelings and behaviors
Drugs
MDMA
aka “ecstasy” or “molly”
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List some complications due to hallucinogen use:
Varied complications depending on type of hallucinogen.
- major hallucinogens seem to have low addiction potential
- LSD - relatively few side effects (though some report long-lasting visual changes)
- MDMA - long-term use may cause problems with mood and cognitive performance, and long-lasting changes in patterns of brain activation
List recreational uses, possible clinical uses and action in brain for:
Psilocybin/psilocin
(according to archaelogical evidence this was used in prehistory)
aka Psilocybe mushroom
Action in brain:
- Partial agonist of 5-HT receptors, especially 5-HT2A receptors that occur in high density in visual cortex
- modifies activity of frontal and occipital cortex
Recreational use(s) (as reported by users):
- feelings of transcendence
- spiritual experiences
- intense visual experiences
- alterations in perception of time
- NOTE: exact effects are strongly influenced by environment and user expectations
Potential clinical application(s):
- improvements in OCD symptoms
- cluster headache (a type of migraine)
- treatment-resistent depression
- debilitating anxiety/anxious (ex. terminal cancer patients)
3.6(p110) Table 3.4 Possible Clinical Applications for Hallucinogens
List recreational uses, possible clinical uses and action in brain for:
lysergic acid diethylamide (LSD)
aka “acid”
Action in brain:
- activates many subtypes of monoamine receptors, esp. DA and 5-HT
- this results in heightened activity in many cortical regions, especially frontal, cingulate, and occipital cortex
Recreational use(s):
- produces pronounced perceptual changes resembling hallucinations
- intense colors in geometric patterns
- novel visual objects
- altered sense of time
Possible Clinical Application(s):
- treatment of alcoholism and other additions
- may be effective treatment for some types of debilitating anxiety
3.6(p110) Table 3.4 Possible Clinical Applications for Hallucinogens
List recreational uses, possible clinical uses and action in brain for:
Ketamine
aka “Special K”
Action in brain:
- widespread effects, especially blockade of NMDA receptors
- stimulates opioid and ACh receptors
Recreational use(s):
- creates detached, trancelike state (in keeping with its medical use as anesthetic)
- may also produce hallucinogenic perceptual alterations
Possible Clinical Application(s):
- at low doses, may be effective antidepressant, even in treatment-resistant cases
3.6(p110) Table 3.4 Possible Clinical Applications for Hallucinogens
List recreational uses, possible clinical uses and action in brain for:
3,4-Methylenedioxymethamphetamine (MDMA)
aka “ecstasy”
Action in brain:
- stimulates release of monoamine transmitters and prosocial hormone oxytocin
Recreational use(s):
- intense visual phenomenon
- empathy
- strongly prosocial feelings
- euphoria
Possible Clinical Application(s):
- may reduce PTSD symptoms, especially in combo with conventional psychotherapy
- still some drug safety concerns
3.6(p110) Table 3.4 Possible Clinical Applications for Hallucinogens
Alcohol use disorder is characterized by the DSM-5 as “a problmatic pattern of alcohol use leading to clinically significant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period:
- alcohol is often taken in larger amounds or over longer period than intended
- persistent desire or unsuccessful efforts to cut down/control alcohol use
- much time is spent in activities necessary to obtain/use/recover from alcohol/its effects
- craving, strong urge to use alcohol
- recurrent alcohol use resulting in failure to fulfill role obligations at work, home, school
- continued alcohol use despite persistent/recurrent social or interpersonal problems caused or worsened by alcohol effects
- important social, occupational, or recreational activities are given up or reduced bc of alcohol use
- recurrent use in situations where it’s physically hazardous
- use is continued despire knowledge of having persistent physical or psych problem likely to have been caused or exacerbated by alc
- tolerance as defined by either: need for markedly increased amounts of alc to achieve intoxication or desired effect OR markedly diminished effect with cntd use of same amount of alc
- Withdrawal, as manifested by either: characteristic withdrawal syndrome for alc (listed elsewhere in DSM) OR alcohol/related substance taken to relieve or avoid withdrawal symptoms
3.7(p112) Table 3.5
What are the four major models of substance abuse?
- moral model
- disease model
- physical dependence model
- positive reward model
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Explain the moral model of substance use.
The moral model blames substance use on weakness of character and lack of self-control.
Proponents may apply exhortation, peer pressure, religion to curb abusive practices.
Limited success, are not founded in scientific framework to address neurobiological roots of addiction.
Examples: temperance movement; D.A.R.E.
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Explain the disease model of substance use disorders.
According to the disease model, a person who abuses drugs requires medical treatment rather than moral exhortation or punishment. This model appeals to many and much research is focused on looking for pathological states that create addiction after initial exposure to drug.
Issue with this is that:
- substance abuse is unlike other diseases. “Disease” is generally reserved for a case involving physical abnormality, and there is no such case in substance use addictions.
- offers no clue about how addiction arises
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Explain the physical dependence model of substance use disorders.
Argues that people keep taking drugs in order to avoid withdrawal symptoms. Model does a good job of explaining why addicts will go to great lengths to obtain the drug they are addicted to.
Issues with this model:
- does not explain how addiction becomes established in the first place
- why do some people abuse drug before tolerance is developed?
- why do some people become addicted to some drugs even when there are minimal physical withdrawal symptoms? (ex. cocaine is powerfully addictive and produces intense drug craving but cocaine withdrawal is not accompanied by severe physical symptoms seen in other highly addictive drugs)
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Explain the positive reward model of substance use disorders.
proposes that people get started with drug abuse and become addictive because the abused drug provides powerful reinforcement
Examples: animals repeatedly lever-pressing in order to receive small dose of addictive drug like cocaine or morphine
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withdrawal symptoms
dysphoria
What is considered to be the most probable model for explaining addiction?
Positive reward model
a region of the forebrain that receives dopaminergic innervation from the ventral tegmental area, often associated with reward and pleasurable sensations
many addictive drugs cause the release of dopamine in this region
nucleus accumbens
Which pathway do many drugs of abuse activate, producing rewarding sensations?
dopaminergic pathway
various pleasurable activities (sex, shopping, games, exercise, gambling) activate this pathway. These activties “reward” may be eclipsed if an individual uses drugs, since certain drugs activate the dopaminergic pathway so strongly.
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A region of cortex lying below the surface, within the lateral sulcus, of the frontal, temporal and parietal lobes.
This region appears to play an important role in addiction, craving, and pleasure.
Shrinkage of the left ——– is observed in people addicted to various substances.
insula
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List strategies to treat addiction through medicine (and examples of medicines).
- Lessening discomfort of withdrawal and drug craving (benzodiazepenes/other sedatives, anti-nausea meds, sleep meds; TMS also may reduce drug hunger/relapse rates)
- providing an alternative to the addictive drug (agonists/partial agonist analogs of the addictive drug weakly activate same mechanisms to help wean person; ex. methadone, nicotine patch)
- directly blocking actions of the addictive drug (specific receptor antagonisists; ex. Narcan)
- altering metabolism of addictive drug (changing drug’s breakdown to reduce or reverse rewarding properties; ex. Disulfiram changes alc metabolism such that nausea-inducing metaobolite - acetaldehyde - accumulates)
- blcoking brain’s reward circuitry (ex. dopamine receptor blockers; can blunt activity of mesolimbocorticol DA reward system but also cause anhedonia)
- immunization to render the drug ineffective (vaccines against cocaine, heroin, and meth have been developed and are in testing)
3.7(p116) - Figure 3.17
