Exam 2 Flashcards
What is a neurotransmitter?
Chemical released onto target cell
Criteria for neurotransmitters
- Substance exists in presynaptic axon terminals
- Substance synthesized in presynaptic cells
- Substance released when action potential reaches axon terminals
- Receptors for the substance exist on postsynaptic membrane
- When applied, substance causes changes in postsynaptic cell
- Blocking substance release prevents changes
If a neurotransmitter does not follow all of the criteria for neurotransmitters, what is it called?
Atypical neurotransmitter (violate at least one rule that is a criteria for neurotransmitters)
Name the types of typical neurotransmitters
Amino acid neurotransmitters, amine neurotransmitters, peptide neurotransmitters
Amino acid neurotransmitter examples
GABA (gamma-aminobutyric acid), Glutamate, Glycine
What do all amino acids have?
NH2 and COOH
Amine neurotransmitters
Based on modifications of a single amino acid nucleus
Peptide neurotransmitters
Based on multiple amino acids/short chains of amino acids
Atypical neurotransmitter type and examples
Gas and lipid neurotransmitters such as nitrous oxide
Name some nearly ubiquitous nts
Glutamate: fast depolarization/excitation, GABA/glycine: inhibitory/causes hyperpolarization
True or false: we can study brain tissue in a way such that only neurons responsible for making a certain neurotransmitter are present/labled
True
How many neurotransmitters does a neuron make?
Typically only 1
Why is it easy for diseases like Alzheimer’s and parkinson’s to occur?
Pathways are based on a relatively small number of neurons/nerves
Describe the cholinergic pathway
Basal forebrain to hippocampus, cortex, and amygdala. . In the peripheral nervous system, acetylcholine is present at the neuromuscular junction and in the central nervous system, ACh has different effects including
- Reward system (which nicotine activates by activating NACh receptors on the brain’s surface
- When acetylcholine binds to specific neurons in the VTA it releases dopamine
- Muscarinic acetylcholine receptors: cognition, so blockers can produce hallucinations; they aid in transduction of cholinergic signals and are GPCR’s
Dopaminergic pathway
Two pathways
- Mesolibocortical pathway: VTA to NAcc and cortex, especially important for processing reward, and abnormalities are associated with some symptoms of schizophrenia
- That is why antipsychotics typically target DA receptors
DA is important for learning shaped by positive reinforcement
Mesostriatal pathway- substantia niagra to basal ganglia
- neurons in niagra release dopamine in striatum and innervate the striatum
- loss of neurons associated with parkinson’s
Serotonergic
Midbrain raphe nuclei to forebrain
Brainstem raphe nuclei to spinal cord
Cell bodies mainly found in nuclei then they spread all over
Serotonin is implicated in sleep, mood, sexual behavior, anxiety which is why drugs like prozac increase amount of 5HT in synaptic cleft to increase receptor activity
Noradrenergic
Norepinephrine/noradrenaline
- Alertness, mood, sexual behavior
- Locus coeruleus to forebrain
- Lateral tegmented area to brainstem/spinal cord
Axons from these areas spread through cerebrum including cerebral cortex, limbic system, and thalamic nuclei
Glu
Glutamate
Gly
Glycine
ACh-
Acetylcholine
DA
Dopamine
NE
norepinephrine
5-HT
serotonin
How do we identify and name neurotransmitters?
Look at which nt it bonds, whether it is ionotropic or metabotropic, and whether there is specific pharmacology/special drugs that bind/affect it
Drugs can be used to find specific functions of certain molecules
True
What is a drug?
An exogenous substance w/biological activity that is not food or water, it may have different modes of activity
Agonist
Activates response of the receptor
Antagonist
Inhibits activity, either by blocking or by preventing bonded neurotransmitter from having an effect
Ligand
A substance that binds to a receptor and effects it
Agonist
A substance that binds to a receptor and initiates/activates a response of the receptor
Antagonist
A substance that reduces receptor activation by other ligands
What are the 2 types of agonists?
Competitive and noncompetitive, where competitive bond to site and prevent endogenous ligand from binding to ion channel and noncompetitive where ligand does not bind to site but still blocks activation of the receptor
What effect can nts have on ionotropic receptors
can either open or close the ion channel and in metabotropic receptors, g protein is activated
Is the dose-response curve on a log scale? if so, why?
Yes it is, and this is so that equal weight is given to both sides of the curve visually speaking
What is the DRC?
A cumulative histogram measuring %response based on dose of a drug
ED50
Dose at which 50% of patients respond/produce a specified effect
True or false: a higher ed 50 means the drug is more potent
False because a higher ed 50 means it takes more of the drug to achieve the desired effect
What is the therapeutic index?
A ratio comparing the ED 50 and LD50 of a drug; wide therapeutic index represents a large difference between average effective and average lethal dose
LD50/TD50
Dose that causes 50% of patients to die or to produce an adverse effect
What causes an effective or lethal dose to change for a patient over time?
Drug tolerance- can develop over time so that successive treatments have less of an impact
Metabolic tolerance
Organs like the liver become better at eliminating the drug from the bloodstream before it even has an effect
Functional tolerance
Tissue target changes its physiology in response to the drug
After repeated doses of an agonist drug, what may happen?
Fewer receptors present on the surface of the cell so that there are fewer chances for the agonist to have an impact
After repeated doses of an antagonist drug, what may happen?
Drug may upregulate+increase number of receptors which makes it more difficult for the antagonist to continue inhibiting receptor function
What drug does opium contain?
Morphine
What does mophine do and what part does it target?
Analgesic and painkiller, targets endogenous opiate receptors and acts as an agonist
True or false: opiate drugs like oxycodone, heroin, and morphine are highly addictive
True
How did the opioid crisis establish its roots in the U.S.?
Extended release forms of opiods were manufacured and marketed as a less addictive way of treating chronic pain but crushing the tablets got rid of the extended release idea
What do stimulants do, where do they target? Give examples
Stimulants are a psychoactive drug used to increase awakeness and act as agonists for glutamate and dopamine- caffeine, nicotine, and amphetamine are all common examples
T or F: Adderall, Focalin, and Ritalin is an Amphetamine and a stimulant used to treat ADHD
T
Short term affects of amphetamines
euphoria, alertness, stamina
Long-term effects of amphetamines
sleeplessness, loss of stamina, deterioration of mental and physical condition, may lead to symptoms of schizophrenia
Describe how the meth epidemic may have taken place
Meth fairly easy to synthesize, poor rural areas often have a lot of precursor
LSD
Serotonin/monoamine activator for things like DA and 5HT receptor agonist, derived from ergotamine, leads to hallucinations, may treat depression and anxiety
Psilocybin/mushrooms
Partial 5HT agonist, especially in visual cortex, modifies activity of frontal and occipital cortex, spiritual feeling/hallucinations, may treat anxiety
Ketamine
Blocks NMDA receptors important in learning, stimulates opiate and ach receptors, creates a detached state and can treat depression
MDMA
Release of monoamine neurotransmitters and oxytocin, euphoria, social feelings, can treat ptsd
Antipsychotics
Typical antipsychotics are DA receptor antagonists to help w/paranoia and hallucinations, atypical antipsychotics help address other symptoms such as social withdrawal
Antidepressants
SSRI's and SNRI's- selective serotonin or serotonin norepinephrine reuptake inhibitors, prevent reuptake of serotonin and norepinephrine from synaptic cleft Older less prescribed class is MAOI- monoamine oxidase inhibitors that prevent breakdown of monoamine neurotransmitters but can be fatal
Anaesthetics
May antagonize glutamate, agonize gaba, or affect vcNaC’s, produce numbness and unconsciousness
Depressants
anxiolytic, sedative, hypnotic, targets + agonizes gaba and glycine
Marijuana and cannabinoids
Derived from cannabis sativa, best known psychoactive compound is delta nine or thc, other compounds include cannabinol, cannabidiol,
Tetrahydrocannabivarin
Psychological impacts of cannabis
Some excitatory effects but not considered a stimulant, may produce sedative effects but no risk of coma, can produce pain relief and hallucinations but not really related to hallucinogens or opiates
How were endocannabinoids discovered?
Radiolabeled ligand used, first endocannabinoid called anandamide, most abundand is called 2_AG, cannabinoids are lipid like
Medical uses of weed
Pain relief, antiemetic, anticonvulsant
Which psychoactive drug will be addictive/
Those that create a reward response in brain, drugs that don’t elicit as strongly are less likely to be addictive
Addiction/SUD
preoccupation with obtaining drug, compulsive use despite consequences, high relapse tendency, sustained problems+patterns that interfere with daily life
Substance abuse
Malapidative use of substance for>1 month that doesn’t meet SUD criteria
Tolerance
Person needs more of a drug to be able to achieve same effect
Withdrawal
Negative reaction when drug use stopped
What is addiction/SUD characterized by
rewiriring of reward system; sex, drugs, gambling, shopping can all initiate dopaminergic signalling in brain from VTA onto nacc but Drugs do this way more
How is addiction measured in lab rats?
Catheter inserted and connected to a lever, pushing down lever injects drug
True or false: dopamine levels as a percent of the baseline are much higher for drugs than for other things that elicit natural rewards like food and sex
True, DA levels are with cocaine DA levels were up to 600-700% of baseline compared to 150-200% for food or sex
How does cocaine affect DA levels?
Cocaine prevents reuptake of dopamine so there is more hanging out in the extracellular space
How does amphetamine affect DA levels?
Amphetamine sneaks into the presynaptic terminal and forces the outflow of dopamine
What do addictive drugs do?
Increase output of dopamine from VTA onto nucleus accumbens
What is the ideal qualities for a drug to be addictive?
Fast onset, multiple consumptions of drug needed (this helps reinforce positive reinforcement and learning) so fast onset, low duration is the most addictive drug
Stages of addiction
Use: drug is used, causing dopamine release from vta, allowing for positive reinforcement of drug taking behavior
Tolerance: more of drug needed to achieve same effect
Dependence: instead of being needed to feel good, drug is needed to feel normal
Addiction: continued use of drug despite negative effect
Describe the stages of binge intoxication
binge intoxication, pleasureable effects, abstinence (neutral effect), reward craving
Describe the stages of compulsive stage of drug abuse
prolonged intoxication, relief, prolonged abstinence (negative effect), relief craving
What factors impact drug abuse?
Availability/exposure, intensity, duration, frequency, genetics, stress, withdrawal, reward feeligns
true or false: loss of gray matter from alcohol is irreversible
false, it can be reversed
True or false: alcohol use can lead to buildup of triglycerides (fatty liver) and scarring and impaired liver function (cirrhosis)
true
What deficiencies do cocaine users have
deficiencies in executive functions (prefrontal cortex)
Why is cocaine so addictive?
euphoria and craving
What are some difficulties with addiction treatment
difficult to treat, high relapse rates, no telling which treatments will or won’t work
Behavioral interventions to addiction
immersive rehab, group therapy/anonymous groups, lifestyle changes, individual therapy, maybe cbt, dbt, or rebt as they do seem to alleviate some types of symptoms but relapse rates are still high
Agonistic addiction treatments
mimic effects of drug, like nicotine patch
antagonistic drug treatments
prevent drug’s effects, like baclofen which interferes w/da pathway
Characteristics of invertebrate nervous systems
nerve nets, radial nerves, neural rings, simple ganglia
characteristics of vertebrate nervous systems
central and peripheral nervous systems
Advantages to studying simpler nervous systems
more simple so basic neuronal processes and behaviors can be better studied+understood
common features of vertebrate nervous system
bilateral symmetry, segmentation, hierarchical control, separate peripheral and central nervous systems, distinct localization of specialized functions, develop from hollow dorsal neural tube
six stages of neural development
neurogenesis, cell migration, cell differentiation, synaptogenesis, cell death, synapse rearrangement
3 layers of embryo, which one does nervous system come from?
endoderm, mesoderm, ectoderm (nervous system comes from ectoderm)
steps of formation of nervous system
totipotent cell, pluripotent cell, zygote creates a hollow ball and then dips within itself to form layers (gastrulation), as cell layers thicken they form a grooveand crests come together to form neural tube, interior of tube becomes ventricals, center of spinal cord, and passages,
Parts of developing brain
Spinal cord, robencephalon (pons, medulla, cerebellum), mesencephalon (midbrain), and forebrain (diencephalon- thalamus and hypothalamus) and telencephalon (central hemispheres and olfactory bulbs)
6 stages of neurodevelopment
- neurogenesis, where cells of neural tube divide to form progeny cells, noneuronal cells divide through mitosis and form the ventricular zone, cells leave the ventricular zone and become either neurons or glial cells,
- Cell migration where cells move towards surface and leave ventricular zone, radial glial cells act as guides and cell adhesion molecules promote adhesion to guard cells
- cell differentiation- genes differently expressed so cells specialize
- synaptogenesis- establishment of synaptic connections, neurons extend synapses and dendrites to form connections, growth cones contain filopodia that detect chemical cues to facilitate this
- cell death based on trophic factors- correct connections allow for correct development of trophic factors without these apoptosis occurs
- synapse rearrangement
apoptosis stages
chromatin condensation, nuclear fragmentation, blebbing, cell fragmentation, consumption by phagocytes
What aspects may vertebrate brains vary in?
Size, proportions, anatomical locations
Define what is meant by cortical real estate
the idea that functional regions of the brain vary in size depending on how much the animal uses that function
What factors led to the rise of a large brain?
Hominid brains enlarged rapidly in our recent evolution
Australopithecines were hominids that made and used tools
Ability to use tools reduced the necessity for large jaws and teeth, freeing up brain space for brain growth
as homo erectus evolved, faces got smaller and brain got larger
costs and benefits of large brain
long gestation period
prolonged dependence on parents
high metabolic needs
complex genes prone to mutation
increased survival+ability for group interaction in humans
innovative behavior, use of tools, and social learning in humans
social brain hypothesis
a larger brain is needed to maintain social relationships between similar individuals
circadian rhythm definition
functions of a living organism that display a cycle of about 24 h
what did the hamster do when dark period started later
activity started later
constnat dim light hamster
activity started a little later each day, indicating presence of endogenous clock
true or false- endogenous clocks are 24 hours
false
define entrainment
syncing endogenous clock to external cues like zeitgebers
what is the biological clock and where is it located
suprachiasmatic nucleus in hypothalamus above optic chiasma- lesioned scn shows less periodicity and transplant with 20 hour tau shoes change to tau cycle
how does light info enter human brain
through retinohypothalamic pathway where retinal ganglion cells contain photosensitve melanopsin
molecular basis for clock
neurons in scn make clock and cycle, which combine to form a dimer, which enhances DNA production of per and cry, which combine to inhibit clock and cycle, retinal gsnglion cells detect light and release glutamate which triggers production of per, per and cry eventually degrade, takes about 24 hours for this process to occur and inhibition lifts and process restarts The entire cycle takes about 24 hours to complete, and it is this 24-hour molecular cycle that drives the 24-hour activity cycle of SCN cells. Each SCN neuron uses this mechanism to keep time approximately, and then the neurons communicate with each other through electrical synapses (see Chapter 3), synchronizing their activity to produce a very consistent period of about 24 hours (Long et al., 2005). That period then drives circadian processes throughout the body.
