Ch. 3 Flashcards
Chapter 3 of The Mind's Machine
Exogenous
arising from outside the body
Endogenous
produced inside the body
Presynaptic
transmitting side of the synapse
What happens at upon the arrival of the action potential?
- action potential strongly depolarizes the axon terminal
- voltage-gated calcium (Ca2+) channels in the terminal membrane open
- inflow of Ca2+ ions
- migration of synaptic vesicles to the nearby presynaptic membrane, where specialized proteins on the walls of the vesicles and corresponding proteins on the synaptic membrane interact and cause the vesicles to release their cargo of molecules of neurotransmitters into the synaptic cleft
- neurotransmitter molecules briefly bind to their corresponding neurotransmitter receptors
- neurotransmitter molecules must be cleared from the synapse
Neurotransmitter receptors
protein molecules embedded in the postsynaptic membrane that recognize a specific transmitter– which then mediate a response on the postsynaptic side
How are neurotransmitter molecules cleared from the synapse?
Either (1) broken down by enzymes into simpler chemicals (2) brought back into the presynaptic terminal in a process called reuptake– relies on transporters
Transporters
A specialized membrane component that returns transmitter molecules to the presynaptic neuron for reuse. Neurotransmitter molecules can then be recycled
What are the two categories of neurotransmitter receptors?
- Ionotropic receptor- ion channel that changes shape (either opens or closes) when bound by a neurotransmitter molecule. Allows for more or fewer ions to flow into or out of the postsynaptic neuron, changing the local membrane potential
- Metabotropic receptor- (does not contain ion channels) when activated, uses a second-messenger system to open nearby ion channels or may kick off a chain of chemical reactions that affect gene expression
Excitatory Synapse
A type of synapse that, when active, causes a local depolarization that increases the likelihood the postsynaptic neuron will fire an action potential
Inhibitory Synapse
A type of synapse that, when active, causes a local hyperpolarization that decreases the likelihood the neuron will fire an action potential
Receptor Subtypes
Any type of receptor having functional characteristics that distinguish it from other types of receptors for the same neurotransmitter
G protein–coupled receptors (GPCRs)
A type of receptor that, when activated extracellularly, initiates a G protein signaling mechanism inside the cell
What is the specific response of any postsynaptic neuron to molecules of neurotransmitter determined by?
the particular subtypes of receptors presented on the postsynaptic membrane
Acetylcholine (ACh)
A neurotransmitter that is produced and released by parasympathetic postganglionic neurons, by motor neurons, and by many neurons in the brain
What are some basic principles that qualifies a brain chemical as a neurotransmitter?
-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.
-It causes changes in the postsynaptic cell.
-Blocking its release interferes with the ability of the presynaptic cell to affect the postsynaptic cell.
Amino Acid Neurotransmitters
A transmitter that is itself an amino acid. Examples include GABA, glycine, and glutamate
Peptide Neurotransmitters
A neurotransmitter consisting on a short chain of amino acids
Amine Neurotransmitters
A neurotransmitter based on modifications of a single amino acid nucleus. Examples include acetylcholine, serotonin, and dopamine
Gasotransmitters
A neurotransmitter that is soluble in gas. Examples include nitric oxide and carbon monoxide
Glutamate
An amino acid transmitter; the most common excitatory transmitter
Gamma-aminobutyric acid (GABA)
A widely distributed amino acid transmitter, the main inhibitory transmitter in the mammalian nervous system
Co-localization
The synthesis and release of more than one type of neurotransmitter by a given presynaptic neuron
Basal Forebrain
A region in the forebrain, ventral to the basal ganglia, that is the major source of cholinergic projections in the brain. It has also been implicated in sleep.
Cholinergic
referring to cells that use acetylcholine as their synaptic transmitter
Widespread loss of cholinergic neurons is associated with what?
Alzheimer’s disease
What are the two families of ACh receptors in the peripheral and central nervous system?
nicotinic and muscarinic
What is the characteristics of nicotinic receptors?
-quick-acting
-ionotropic
-excitatory
-drives muscle contractions
-drugs that block nicotinic acetylcholine receptors cause widespread paralysis
What are some characteristics of muscarinic receptors?
-slower
-can be either excitatory or inhibitory
-crucial in widely varying cognitive processes
Dopamine (DA)
A monoamine transmitter found in the midbrain–especially the substantia nigra–and in the basal forebrain
Dopaminergic
referring to cells that use dopamine as their synaptic transmitter
Mesostriatal Pathway
Dopaminergic projection that originates in the midbrain (mesencephalon) around the substantia nigra and projects axons to the basal ganglia
Substantia Nigra
A brainstem structure that innervates the basal ganglia and is a major source of dopaminergic projections to the basal ganglia
What happens when people lose a significant amount of mesostriatal dopaminergic neurons?
develop the profound movement problems of Parkinson’s disease
Mesolimbocortical Pathway
A major dopaminergic projection that originates in a midbrain region called the ventral tegmental area (VTA) and projects to various locations in the limbic system and cortex. Important for the processing of reward; probably where feelings of pleasure arise.
What is the mesolimbocortical pathway useful for?
learning that is shaped by positive reinforcement
Ventral Tegmental Area (VTA)
A portion of the midbrain that projects dopaminergic fibers to the nucleus accumbens
What does abnormalities in the mesolimbocortical pathway result in?
symptoms of schizophrenia
Serotonergic
referring to cells that use serotonin as their synaptic transmitter
Where are serotonergic fibers?
They originate from neurons sprinkled along the midline of the midbrain and brainstem in the raphe nuclei
Raphe Nuclei
A string of nuclei in the midline of the midbrain and brainstem that contain most of the serotonergic neurons of the brain
What is the function of serotonin 5-HT?
participates in the control of all sorts of behaviors: mood, vision, sexual behavior, anxiety, sleep, and many other functions
Noradrenergic
referring to cells using norepinephrine as a transmitter
Norepinephrine (NE)
Also called noradrenaline. A neurotransmitter produced and released by sympathetic postganglionic neurons to accelerate organ activity
Where are the cell bodies of norephinephrine?
regions of the brainstem and midbrain: the locus coeruleus and the lateral tegmental area
Locus Coeruleus
A small nucleus in the brainstem whose neurons produce norepinephrine and modulate large areas of the forebrain
Lateral Tegmental Area
A brainstem region that provides some of the norepinephrine-containing projections of the brain
Opioid Peptides
A type of endogenous peptide that mimics the effects of morphine in binding to opioid receptors and producing marked analgesia (painkiller) and reward.
Gut Peptides
act as synaptic transmitters, and are often co-localized with classical transmitters
The hypothalamus and pituitary produce what peptide hormones?
oxytocin, orexin, and vasopressin
In what ways are gasotransmitters (nitric oxide and carbon monoxide) different from traditional neurotransmitters?
- not held in vesicles, not produced in axon terminals, substance dissolves in cellular fluids and diffuses out of the neuron as it is produced
- No receptors in the membrane of the target cell are involved. Instead, the gasotransmitter diffuses into the target cell to trigger second messengers inside
- can function as retrograde transmitters by diffusing from the postsynaptic neuron back to the presynaptic neuron, a gasotransmitter conveys info that is sued to physically change the synapse
Retrograde Transmitters
A neurotransmitter that is released by the postsynaptic neuron, diffuses back across the synapse, and alters the functioning of the presynaptic neuron
Ligand
any substance that binds to a receptor
Agonists
Drugs that mimic or potentiate the actions of a transmitter
Receptor Agonist
A substance that mimics the normal action of a neurotransmitter on its receptors by binding to the receptors and activating them
Antagonists
Drugs that reduce the normal actions of a neurotransmitter system. Receptor antagonists=bind to receptors but do not activate them (block them from being activated by their normal neurotransmitter)
Partial agonists
A drug that, when bound to a receptor, has less effect than the endogenous ligand would
How do drug molecules find their particular receptor molecules?
The drug molecules spread widely throughout the body, binding to their selective receptors when they happen to encounter them
Bioavailable
Referring to a substance, usually a drug, that is present in the body in a form that is able to interact with physiological mechanisms
Biotransformation
The process in which enzymes convert a drug into a metabolite that is itself active, possibly in ways that are substantially different from the actions of the original substance
Pharmacokinetics
Collective name for all the factors that affect the movement of a drug, into, through, and out of the body
Binding Affinity
the propensity of molecules of a drug to bind to receptors
What is the relationship between low doses and binding affinity?
At low doses, when relatively few drug molecules are in circulation, drugs with preferentially bind to their highest-affinity receptors
Efficacy
Also called intrinsic activity. The extent to which a drug activated a response when it binds to a receptor
Agonists vs. antagonists in terms of efficacy
Agonists have high efficacy (activate the receptors they bind to) while antagonists have low efficacy
What determines the action of a drug?
affinity and efficacy- where it binds and what it does
Dose-response Curve (DRC)
A formal graph of a drug’s effects (on the y-axis) versus the dose given (on the x-axis). Reveals useful and safe dosage ranges and is one of the main tools for understanding the functional relationships between drugs and their targets.
What poses a major challenge for neuropharmacology?
the blood-brain barrier because many compounds that could be useful for research or clinical treatment have molecular sizes too large to cross the blood-brain barrier and enter the brain
Drug Tolerance
A condition in which, with repeated exposure to a drug, an individual becomes less responsive to a constant dose. Drug’s effectiveness diminishes with repeated treatments.
Metabolic Tolerance
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 from the bloodstream before it can have an effect
Functional Tolerance
The form of drug tolerance that arises when repeated exposure to the drug causes receptors to be upregulated or downregulated. The target tissue may change its sensitivity to the drug
Downregulate
decrease the number of receptors available to the drug (neuron becomes less sensitive and counters the drug effect). Result of repeated doses of an agonist drug
Upregulate
increase the number or receptors to become more sensitive and thus counteract the drug affect. Result of repeated doses of an antagonist drug
Cross-Tolerance
A condition in which the development of tolerance for one drug causes a development in tolerance for another drug of the same chemical class
Sensitization
A process in which the body shows an enhanced response to a given drug after repeated doses.
The most common presynaptic drug effects can be grouped into three main categories:
effects on transmitter production, effects on transmitter release, and effects on transmitter clearance
What does the presynaptic neuron need to produce a neurotransmitter?
a steady supply of raw materials and enzymes must arrive at the axon terminals and carry out the needed reactions
What are some ways that drugs can affect the production of transmitters?
-Drug may inhibit an enzyme that neurons need in order to synthesize a particular neurotransmitter= depletion of that transmitter
-Drugs can block axonal transport= prevents raw materials from reaching the axon terminals in the first place
What are some ways that drugs can block action potentials from arriving?
-local anesthetics (ex. procaine) block sodium channels and thus clock the action potentials that nearby neurons would’ve used to report pain
-Tetrodotoxin shuts down synaptic transmission throughout the body
-calcium channel blocker drugs block the calcium influx that normally drives the release of transmitter into the synapse
-Active ingredient in Botox (botulinum toxin) block ACh release from axon terminals near the injection site (paralysis of underlying muscles)
-Drugs stimulate autoreceptors provide a false feedback signal, prompting the presynaptic cell to release a transmitter
-Drugs block autoreceptors to prevent presynaptic neuron from receiving normal feedback=cell releases more transmitter than usual
Autoreceptors
A receptor for a synaptic transmitter that is located in the presynaptic membrane and tells the axon terminal how much transmitter has been released
Caffeine
A compound found in coffee and other plants that exerts a stimulant action by blocking adenosine receptors. By blocking presynaptic adenosine receptors, caffeine increases the amount of neurotransmitter released, resulting in the enhanced alertness for which coffee is renowned
What are some ways that drugs can affect transmitter clearance?
-reuptake inhibitors work by blocking the presynaptic system that normally reabsorbs transmitter molecules after their release=transmitter molecules stay longer in the synaptic cleft=greater effect on the postsynaptic cell
-block the enzymes that normally break up molecules of transmitter into active metabolites
What are the two major classes of postsynaptic drug actions?
- direct effects on transmitter receptors
- effects on cellular processes within the postsynaptic neuron
What are some ways that drugs can affect postsynaptic transmitter receptors?
-antagonists bind directly to postsynaptic receptors and block them from being activated by their neurotransmitter. Ex. curare blocks nicotinic ACh receptors found on muscle=paralysis of al skeletal muscles
-selective receptor agonists bind to specific receptors and activate them, mimicking the natural neurotransmitter at those receptors. Ex. LSD stimulates a subtype of serotonin receptors found in visual cortex
First-generation Anitpsychotics
Any of a class of antipsychotic drugs that alleviate symptoms of schizophrenia, typically by blocking dopamine receptors
What are some examples of first-generation drugs? And what do they have in common?
chlorpromazine (thorazine), haloperidol (haldol), and loxapine (loxitane). They all act as selective antagonists of dopamine D2 receptors of the brain
Second-generation Antipsychotics
An antipsychotic drug that has primary actions other than or in addition to the dopamine D2 receptor antagonism that characterizes the first-generation antipsychotics. Usually the blockade of certain serotonin receptors.
Anitdepressant
Drugs that act to increase synaptic transmission. Examples include monoamine oxidase (MAO), tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), serotonin-norephinephrine reuptake inhibitors (SNRIs).
How does monoamine oxidase (MAO) function?
blocks the enzyme responsible for breaking down monoamine transmitters such as dopamine, serotonin, and norepinephrine. This allows transmitter molecules to accumulate in the synapses for improvement in mood.
How does tricyclic antidepressants function?
Promotes an accumulation of synaptic transmitter by blocking the reuptake of transmitter molecules into the presynaptic terminal
How does selective serotonin reuptake inhibitors (SSRIs) function?
Also increases synaptic transmitter availability, but they focus on specific neurotransmitters. Examples include fluoxetine (Prozac) and citalopram (Celexa) act to specifically block reuptake at serotonergic synapses.
How do serotonin-norepinephrine reuptake inhibitors (SNRIs) function?
Promotes the accumulation of both serotonin and norepinephrine, by blocking reuptake of both. Useful for more mental disorders that just depression, also useful for anxiety disorders
Depressants
A drug that reduces the excitability of neurons
Barbiturate
An early anxiolytic drug and sleep aid that has depressant activity in the nervous system. They are very addictive and easy to overdose on. Ex. phenobarbital
Anxiolytics
antianxiety drugs
Ex. benzodiazepines
Benzodiazepines
Any class of anti anxiety drugs that are non competitive agonists of GABAA receptors in the central nervous system. Ex. alprazolam (Xanax) and lorazepam (Ativan). Said another way, benzodiazepines bind to specific sites on GABAA receptors and enhance the activity of GABA=GABA produces larger inhibitory postsynaptic potentials than GABA would alone=reduction in the excitability of neurons
Opium
An extract of the opium poppy. Drugs based on opium–morphine, oxycodone, fentanyl–are potent painkillers
Analgesic
painkiller
Morphine
the major active substance in opium that is a very effective analgesic
Heroin (diacetylmorphine)
An artificially modified, very potent form of morphine
Opioid Receptors
A receptor that responds to endogenous or exogenous opioids such as morphine, heroin, and codeine
Periaqueductal Gray
A midbrain region involved in pain perception. It contains a high density of opioid receptors and is an important target because this is where opiates exert much of their painkilling effects
Endogenous Opioids
Any class of opium-like peptide transmitters that have been referred to as the body’s own narcotics. The three kinds are enkephalins, endorphins, and dynorphins
Cannabis
A psychoactive plant containing numerous active compounds in varying proportions. Active ingredients include compounds of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Usually produces pleasant relaxation and mood alteration, although the drug can occasionally cause stimulation and paranoia instead
Delta-9-Tetrahydrocannabinol (THC)
Thought to produce the feeling of being high most closely associated with cannabis use
Cannabidiol (CBD)
Appears to have anxiolytic effects as well as other medicinal actions
Cannabinoid Receptors
A receptor that responds to endogenous and/or exogenous cannabinoids. Two subtypes: CB1 and CB2 that mediate the effects of compounds like THC
Where are cannabinoid receptors found?
the substantia nigra, the hippocampus, the cerebellar cortex, and the cerebral cortex
Endocannabinoids
THC-like endogenous ligands. Ex. anandamide
Anandamide
An endogenous substance that binds the cannabinoid receptor molecule. Produces some of the most familiar physiological and psychological effects of cannabis use: elevated mood, pain relief, lowered blood pressure, relief from nausea, and more
Stimulant
A drug that enhances the excitability of neurons. Alerting, activating effect. Ex. caffeine, nicotine, amphetamine, and cocaine
Nicotine
A compound found in plants, including tobacco, that acts as an agonist on a large class of cholinergic receptors. Acts as a stimulant, increasing heart rate, blood pressure, digestive action, and alertness
Cocaine
A drug of abuse, derived from the coca plant, that acts by enhancing catecholamine neurotransmission. Works by blocking the reuptake of monoamine transmitters–especially dopamine and norepinephrine
What are the risks associated with cocaine?
stroke, psychosis, loss of gray matter in frontal lobes, and severe mood disturbances
Amphetamine (speed)
Drug that induces an accumulation of the synaptic transmitters norepinephrine and dopamine. Happens by amphetamine acting within axon terminals to cause a larger-than-normal release of neurotransmitter when the synapse is activated. Then, amphetamine interferes with the clearance of the released transmitter by blocking its reuptake and metabolic breakdown. Due to this, the affected synapses become unnaturally potent and have strong effects on behavior
Short term effects of amphetamine
increased vigor and stamina, wakefulness, decreased appetite, and feelings of euphoria
What is a similar but more potent drug to amphetamine?
methamphetamine (meth)
What are some effects of prolonged use of amphetamine or methamphetamine?
-symptoms that resemble those of schizophrenia: compulsive, agitated behavior and irrational suspiciousness
-neglect of diet and basic hygiene, aging rapidly
-peripheral effects: high blood pressure, tremor, dizziness, sweating, rapid breathing, and nausea
Khat
An African shrub that, when chewed, acts as a stimulant. Releases amphetamine-like stimulants called cathinones when chewed.
Does alcohol act as a stimulant or a depressant?
both, at first it acts as a stimulant, and then it has a more prolonged depressant phase
How does alcohol function?
It inhibits neural excitability in multiple brain regions via an action on GABA receptors. Also activates dopamine-mediated reward system of the brain.
What are the short term effects of alcohol?
social disinhibition, poor motor control, and sensory disturbances (drunkenness)
What are the consequences in a fetus of an expectant mother drinking alcohol?
fetal alcohol spectrum disorder (FASD), lower fetal weight, preterm birth, changes in craniofacial development, and later behavioral problems
Fetal Alcohol Spectrum Disorder (FASD)
Developmental disorder that varies in severity, resulting from fetal exposure to alcohol consumed by the mother. In severe cases, it included characteristic intellectual disability and facial abnormalities
What are consequences in the brain resulting from heavy drinking?
pathological changes in white matter pathways, decreased volumes of regions in the brain (frontal, temporal, and cingulate cortex, hippocampus, diencephalon, and cerebellum). Results in cognitive decline, memory impairment, and movement disorders
Psychedelics
Also called hallucinogens or entheogens. Drugs that alter sensory perception and produce peculiar experiences
LSD
Also called acid. A psychedelic drug the produces bizarre and mysterious sensory experiences
Why is the name hallucinogens a misnomer?
Because a hallucination is a novel perception that takes place in the absence of sensory stimulation but psychedelics amostly alter or distort existing perceptions
What is the most important shared neural action of many psychedelics?
the stimulation of serotonin receptors
What is the function of LSD?
LSD activates serotonin 5HT2A receptors that are found in especially heavy concentrations in the visual cortex
What are the short term effects of psychedelics?
perceptual effects, mood changes, introspective states, and feelings of creativity
How does Ketamine function?
blocks NMDA receptors and increases activity in the prefrontal cortex and hippocampus and produces feelings of depersonalization and detachment from reality
MDMA
Also called ecstasy or molly. It is a psychedelic amphetamine derivative. MDMA stimulates 5-HT2A receptors in visual cortex and changes levels of serotonin, dopamine, and certain hormones, such as prolactin and oxytocin
What are the short term effects of MDMA?
positive emotions, empathy, euphoria, a sense of well-being, and colorful visual phenomena
Moral Model
Blames disordered substance use on weakness of character and lack of self-control. Proponents of this view may apply exhortatio, peer pressure, and/or religious intervention in an attempt to curb abusive practices.
The Disease Model
Takes the view that people with substance use disorders require medical treatment rather than moral exhortation or punishment
The Physical Dependence Model
Argues that people keep taking drugs in order to avoid unpleasant withdrawal symptoms. Does include how the addiction becomes established in the first place
Withdrawal symptoms
An uncomfortable symptom that arises when a person stops taking a drug that they have used frequently, especially at high doses
Dysphoria
Unpleasant feelings;opposite of euphoria
The Positive Reward Model
Proposes that people may start taking a drug, and become addicted to it because the drug provides powerful reinforcement
Nucleus Accumbens
A region of the forebrain that receives dopaminergic innervation from the ventral tegmental area, often associated with reward and pleasurable sensations
What is the relationship between the dopaminergic pathway and addiction?
If the dopaminergic pathway from the VTA to the nucleus accumbens serves as a reward system for a wide variety of experiences, then the addictive power of drugs may come from their extra strong stimulation of this pathway.
Insula
A region of cortex lying below the surface, within the lateral sulcus, of the frontal, temporal, and parietal lobes
The insula in the folds of the frontal cortex plays an important role in what?
addiction, craving, and pleasure
Abnormalities of the insula is associated with what?
addiction to numerous substances
What are some biological risk factors of addiction?
being male, heritable tendencies to addiction, poor family life, personality factors (poor emotional control), and environmental factors (living in a neighborhood with high rates of addiction)
