Exam 2 Flashcards
(274 cards)
1
Q
encephalon
A
the brain
2
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structures in the forebrain
A
telencephalon, diencephalon
3
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structures in the telecephalon
A
neocortex, basal ganglia, limbic system
4
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structures in the diencephalon
A
thalamus, hypothalamus
4
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mesencephalon
A
midbrain
5
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structures in the hindbrain
A
metencephalon, myelencephalon
6
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structures in the metencephalon
A
cerebellum, pons
7
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myelencephalon
A
medulla
8
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brainstem
A
midbrain, pons, medulla
9
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major striatum components
A
nucleus accumbens, caudate nucleus, putamen
10
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caudate nucleus
A
dorsomedial striatum
11
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putamen
A
dorsolateral striatum
12
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function of nucleus accumbens (core and shell)
A
pleasure, motivation, reward cues
13
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major target of dopamine axon terminals
A
striatum
14
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dopamine neurons in the striatum
A
no DA neurons in the striatum; cell bodies are in the brainstem and send axon projections into the striatum
15
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monoamine neurons
A
dopamine, serotonin, norepinephrine
16
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monoamine neurons in the brain
A
primarily in the brainstem; cell bodies in the brainstem and send axon projections throughout the brain
17
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dopamine neuron locations
A
in the substantia nigra and ventral tegmental area
18
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nigrostriatal pathway
A
dopamine neurons in the substantia nigra send axon projections to the dorsal striatum
19
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mesolimbic pathway
A
dopamine neurons in the VTA send axon projections to the nucleus accumbens and amygdala
20
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mesocortical pathway
A
DA neurons in the VTA send axon projections into the prefrontal cortex
21
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basal ganglia circuits/loops are important for:
A
voluntary movement, action selection, procedural learning, habits
22
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input structures for the basal ganglia
A
cortex; glutamatergic/excitatory
23
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output structures for basal ganglia
A
GPi, SNr; GABAergic/inhibitory
24
striatum projections are...
GABAergic
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direct striatum projection
excites target of basal ganglia output, "go"
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indirect striatum projection
inhibits targets of basal ganglia output, "no-go"
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feedback for basal ganglia
provided by thalamus and midbrain dopamine
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GABA neurons in striatum
half express D1 receptor, half express D2
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D1 neurons
part of direct pathway "go," excited by dopamine
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D2 neurons
part of the indirect pathway, "no-go," inhibited by dopamine
31
common property of addictive drugs
increase dopamine (but through different mechanism)
32
components of reward learning
liking, wanting, reward prediction
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liking
pleasurable aspect of reward, does not involve dopamine
34
wanting
motivational drive to work for rewards, involves DA
35
reward prediction
involves DA
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reward prediction: unexpected reward
increase in DA firing
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reward prediction: response to CS
increase in DA firing when CS presented, not the reward itself
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reward prediction: CS + no reward
decrease in DA firing
39
positive prediction error
reward is greater than expected
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negative prediction error
reward is less than expected
41
positive prediction error effects
activates D1 cells (Gs coupled) and direct pathway
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negative prediction error effects
activates D2 cells (Gi coupled) and indirect pathway
43
properties of a drug that can cause addiction
- route of administration
| - increased lipid solubility
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individual differences that can cause addiction
genes, environment, and the interaction between the two
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genetic factors that increase addiction likelihood
- high impulsivity
| - history of stress or trauma
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genetic factor that decreases addiction likelihood
environmental enrichment
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impulsivity in meth abusers
decreased D2 receptor availability in the striatum correlated with higher impulsivity
48
impulsivity in rats
high level of premature responding shows decreased D2 binding in ventral striatum
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impulsivity and cocaine
high-impulsivity rats will self-administer more cocaine; indicated impulsivity may be a pre-existing condition for addiction
50
stress
influences all aspects of addiction process (drug taking, vulnerability to addiction, relapse)
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stress: enhanced vulnerability
history of social defeat stress shows enhanced place preference for low-dose cocaine
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environmental enrichment
reduced conditioned place preference for cocaine
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prefrontal cortex (PFC)
behavioral inhibition, self-control, executive function
54
nucleus accumbens (ventral striatum)
reward, motivation, cues
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dorsomedial striatum (DMS)
goal-directed learning
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dorsolateral striatum (DLS)
habit learning
57
habit behavior is what type of association?
stimulus-response association
58
goal directed behavior is what type of association?
response-outcome association
59
chronic stress causes:
- enhanced habit learning
- loss of PFC volume
- reduced dendritic complexity
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chronic stress affects striatum:
changes neuronal density in dorsal striatum → DLS more dominant that DMS
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drug-induced neural adaptations
- sensitization of drug effects
- enhanced habit learning
- reduced behavioral inhibition
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enhanced drug motivation experiment
intermittent cocaine use followed by abstinence → increased cocaine potency and drug motivation
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habit learning
history of cocaine exposure to habitual learning
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behavioral inhibition: resistance to negative consequences
some rats continue to self-administer cocaine despite getting footshock, resistant to punishment
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behavioral inhibition: role for PFC
- optogenetic stimulation of PFC restores sensitivity to footshock
- optogenetic inhibition of PFC makes animals resistant to footshock
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drug class of cocaine and amphetamines
stimulants/psychostimulants/psychomotor stimulants/uppers
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drugs in stimulant category
cocaine, amphetamines, nicotine, caffeine
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properties of cocaine
- psychoactive alkaloid
| - weak base
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natural form of cocaine
- raw coca leaf chewed with lime/ash to increase saliva pH (enhances absorption)
- < 2% cocaine
- absorbed in mouth
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cocaine in 1800s and early 1900s
widely used; doctors and scientists highly praised its properties
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coca paste
- crude extraction from leaves
- ~80% cocaine sulfate
- can only be smoked
- aka "paco" or "basuco"
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cocaine HCl
- crystalline powder
- extracted and purified from coca paste
- very high concentration
- water soluble
- can be taken orally, intranasally, or intravenously; CANNOT be smoked
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cocaine free base
- made from cocaine HCl + water + base
- vaporized and smoked ("freebasing")
- residual can be dangerous and explode with flame
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crack cocaine
- made from cocaine HCl
- baking soda instead of solvent, making it safer
- 75-90% cocaine
- smoked
- led to new cocaine epidemic in 80s-90s
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cocaine products
widely used in many products in the 1800s
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current medical uses for cocaine
local anesthetic effects (Schedule II)
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effects at high doses of cocaine (in the brain)
inhibits voltage-gated Na+ channels (involved in action potentials)
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cocaine absorption and distribution
extremely rapid absorption with smoking/IV
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peak subjective effects for crack cocaine
within ~1-2 mins
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inactive major metabolite in cocaine
benzoylecgonine
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half-life of cocaine
0.5-1.5 hrs
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active metabolite in cocaine
cocaethylene; formed when cocaine and ethanol are ingested simultaneously
83
amphetamines
chemical family of synthetic and natural psychostimulants
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ephedrine
- comes from ephedra or "mormon tea" plant (natural)
- active components: ephedrine and pseudoephedrine
- decongestants
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cathinone
- comes from "qat" or "khat" shrub leaves (natural)
| - commonly chewed
86
bath salts
- synthetic variant of cathinone
- methcathinone ("cat") and mephedrone ("meow meow")
- designer drugs
- DEA schedule I
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timeline of use of amphetamines and methamphetamines
1920s-30s: medical use developed
40s: widespread adoption b/c of WWII
early 70s: peak use of "speed"
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first uses of amphetamines/methamphetamines
- benzadrine inhaler (for congestion)
| - narcolepsy
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forms of synthetic amphetamines
D-Amphetamine, L-Amphetamine, Adderall
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route of administration for synthetic amphetamines
typically orally or injection (IV, SC)
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methamphetamines (synthetic)
most potent of amphetamines
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route of administration for methamphetamines
oral, snorted, injected IV, or smoked
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amphetamine-related synthetics
- differ in chemical structure
| - methylphenidate, modafinil
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previous uses for amphetamine
- congestion
- mood and weight control
- fatigue
- increase attention and decrease fatigue in military
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meth epidemic
- easily prepared in common household ingredients
- greater abuse potential
- can be smoked
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current medical uses for amphetamines
- narcolepsy
| - ADD/ADHD
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metabolism and excretion of amphetamines
- slower metabolism and elimination compared to cocaine
| - half-life is 7-30 hours
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stimulants: major effects
- mild to moderate: heightened energy, hyperactive ideation, anger, verbal aggression, inflated self-esteem, etc.
- severe: total insomnia, rambling, incoherent speech, possible extreme violence, delusions of grandiosity
- autonomic effects: increased BP, hyperthermia, bronchodilation
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cocaine vs amphetamines: duration of action
cocaine has a shorter duration of action
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cocaine vs amphetamines: cardiovascular effects
cocaine has worse cardiovascular effects, can be lethal
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cocaine vs amphetamines: seizures
higher convulsive seizure properties in cocaine
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major effects of stimulants in animals
- locomotor activity can appear to decrease with high AMPH doses because rats perform with stereotypy behavior instead
- reinforcing/rewarding effects
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effects of withdrawal
mostly psychological, especially in chronic, high-dose users
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tolerance to some effects of psychostimulants
autonomic and anorexic effects
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sensitization to other effects of psychostimulants
rewarding effects, psychotomimetic effects (psychosis), locomotor stimulant effects
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negative effects of chronic amphetamine use
psychosis, anorexia, physical damage
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history of MDMA
- never used clinically
- can enhance communication and openness
- club drug in 80s-90s
- Schedule I
- taken orally; long-half life (8 hrs)
108
MDMA effects at low doses
- increased empathy and sociability/empathy; mild euphoria
| - increased heart rate and temperature
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MDMA effects at high doses
- mild hallucinogenic effects
| - hyperthermia and dehydration, increased heart rate and blood pressure can lead to stroke
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cocaine as an indirect agonist
blocks reuptake of monoamines (DA, NE, 5-HT)
111
amphetamines as indirect agonists
- cause vesicles to release transmitter
- cause monoamines to be transported out of neuron via reversal of transporter
- results in very high DA in synaptic cleft
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categories of monoamines
catecholamines and indolamines
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catecholamines
dopamine, norepinephrine, epinephrine
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indolamines
serotonin only
115
tyrosine
precursor for catecholamines
116
tyrosine hydroxylase
rate-limiting step in catecholamine synthesis
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all monoamines are one type of neurotransmitter
classical
118
catecholamines are inactivated by
- reuptake via transporters
| - enzymatic degradation
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catecholamine reuptake
- primary mechanism for inactivation
| - much faster than metabolism
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vesicular monoamine transporter VMAT2
packages all monoamines into vesicles
121
each monoamine has their own...
synaptic transporters and receptors
122
enzymes involved in catecholamine metabolism
MAO and COMT
123
D1-like receptors
D1 and D5, coupled to Gs
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D2-like receptors
D2, D3, D4; coupled to Gi
125
presynaptic autoreceptors are mostly what type of receptor
D2
126
area dopamine receptors are primarily concentrated
prefrontal cortex areas
127
monoamine systems
a few thousand neurons in each system send broad, diffuse projections to large areas of the forebrain
128
where the majority of dopamine neurons can be found
substantia nigra and VTA (midbrain)
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nigrostriatal pathway
DA neurons in substantia nigra target dorsal striatum
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mesolimbic pathway
DA neurons in VTA target ventral striatum (nucleus accumbens) and amygdala
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mesocortical pathway
DA neurons in VTA target prefrontal cortex
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dopamine in the striatum
no DA neurons, but has lots of DA fibers, DA release at synapses, and DA receptors/transporters
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classification of dopamine receptors in striatum
half D1, half D2
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cause of parkinson's disease
progressive death of midbrain dopamine neurons and their striatal terminals
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symptoms of parkinson's
- bradykinesia (slow movement)
| - akinesis (frozen) in severe cases
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L-DOPA
can relieve symptoms, but can lead to dyskinesias and other problems
137
drug-induced parkinson's disease
- MPPP+ is a potent DA neurotoxin that can cause parkinson's symptoms within days
- converts MPTP to MAO-B
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MPTP research
used to produce dopamine lesions in non-human primates
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catecholamine neurotoxin
6-OHDA used instead of MPTP to create lesions of catecholamine neurons and/or axon fibers
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drugs that affect DA system
DOPA, 6-OHDA, amphetamine, cocaine, methylphenidate
141
antischizophrenia drugs
D2 antagonists that cause sedation and cataplexy at higher doses
142
4 primary adrenergic receptors are what type of receptor?
all GPCRs
143
alpha-1 adrenergic receptor
coupled to Gq
144
alpha-2 adrenergic receptor
coupled to Gi, serves as autoreceptor
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beta-1 and beta-2 adrenergic receptors
coupled to Gs
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locus coeruleus
major source of NE in the brain, neurons have TH and DBH
147
dorsal noradrenergic bundle (DNAB)
- originates from locus coeruleus
- major source of NE in the brain
- involved in cognition, arousal, and attention
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ventral noradrenergic bundle (VNAB)
- originates from NE neurons in the medulla
| - involved in aversive aspects of stress
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role of NE in stress and arousal
responsible for many stress effects on memory and cognition
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distribution of NE
- central nervous system (brain)
| - major components of peripheral sympathetic nervous system "fight or flight" response
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pharmacodynamics of amphetamine
amph, meth, and MDMA are all agonists of TAAR1 (intracellular GPCR)
152
distribution of cocaine in the human brain
matches that of DA transporters (DAT), which are densest in the striatum
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DA is critical for...
the reinforcing and locomotor effects of cocaine and amphetamines
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antagonists that disrupt amphetamine reinforcement (self-administration)
DA, but not NE
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drugs not readily self-administered by animals or abused by people
- selective blockers of NET
- selective blockers of SERT
- other local anesthetics (Na+ channel blockers)
156
DAT blockade
appears to be the core mechanism by which cocaine and amphetamine are reinforcing
157
lesion studies
using 6-OHDA to lesion DA, but not NE, disrupts cocaine reinforcement (self-administration)
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similar time course for amphetamine effects on:
- DA release in striatum
| - locomotor effects
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repeated amphetamine treatment
- produces sensitization of locomotor and reinforcing effects
- sensitization of DA levels in striatum
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DAT knockout mice
- spontaneously hyperactive
| - show increased locomotion
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DAT knock-in mice
- mutation that makes them DAT insensitive to cocaine
| - show loss of cocaine reinforcement (self-administration)
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Stimulant-induced DA in nucleus accumbens (mesolimbic)
locomotion & reinforcement
163
Stimulant-induced DA in dorsal striatum (nigrostriatal)
stereotypies
164
reward cues and dopamine
- once learned, CS/reward-associated cues will elicit DA release
- drive motivation for reward
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Cue-induced dopamine release in dorsal striatum
correlates with craving in addicts
166
in rats, cocaine-associated cues trigger...
drug seeking
167
treatments for stimulant addiction
- no clinically licensed treatment
| - best treatments are psychosocial, CBT, relapse prevention therapy
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neurotoxicity with amphetamines
Can cause depletion of monoamines and degeneration of nerve terminals
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Amphetamine/methamphetamine neurotoxicity:
- high doses (10-50x)
- high extracellular DA necessary
- amphetamine: damage to DA terminals
- methamphetamine: damage to DA and 5-HT terminals
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MDMA neurotoxicity
- only 2x normal street dose
| - damage to 5-HT terminals
171
methamphetamine neurotoxicity in humans
Long-lasting decrease in DAT availability in abstinent methamphetamine and methcathinone users
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methamphetamine neurotoxicity in baboons
Long-lasting decrease in DAT availability after meth
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methamphetamine neurotoxicity in rats
Long-lasting decreases in TH and DAT after meth
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acute adverse effects of MDMA
- reflect dehydration and hyperthermia
| - subtle cognitive deficits
175
properties of sedative-hypnotics
- depress the CNS and behavior
- anxiolytic properties (downers)
- addictive effects
- cross-dependence and -tolerance
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types of sedative-hypnotics
alcohol, barbiturates, benzodiazepines
177
structurally unrelated drugs similar to sedative-hypnotics
nonbenzodiazepines, methaqualone, GHB, opiates/opioids
178
properties of alcohol
- ethanol (ethyl alcohol) is consumed
- other forms are too toxic
- no current medical use
- not scheduled by the DEA
179
forms of alcohol: fermentation
- natural source
| - yeast fermentation only produces concentrations up to 15%
180
forms of alcohol: distillation
- produces spirits or hard liquor
| - concentration >15%
181
history of alcohol use
- incidence of alcohol abuse increased with distillation
- repeated attempts to ban it (temperance movement, prohibition)
- attempt to ban had opposite intended effects
182
alcohol molecules are ionized/non-ionized
non-ionized
183
% of alcohol absorbed and where
10% absorbed in stomach, 90% in small intestine
184
presence of food in stomach & it's affect on alcohol absorption
- food in stomach slows gastric acid emptying and absorption
| - more alcohol is degraded before being absorbed (first-pass metabolism)
185
small amounts of alcohol eliminated without being transformed
roughly 10% in sweat, tears, urine, and breath
186
breath levels are usually a good indicator of...
blood levels
187
how most alcohol is broken down
alcohol dehydrogenase (ADH) in stomach and liver
188
ADH (alcohol dehydrogenase) individual differences
- affects blood levels of alcohol
| - 60% more gastric ADH in men
189
ALDH individual variation
- affects blood levels of acetaldehyde
| - 50% of certain Asian groups have reduced ALDH function
190
alcohol excretion
zero-order kinetics, cleared at a constant rate
191
blood alcohol content (BAC/BEC)
grams of alcohol per 100 mL of blood
192
person with BAC of 0.2-0.3
quite drunk
193
person with BAC 0.45
LD50 (death), low margin of safety
194
cause of death from alcohol
respiratory centers in the brainstem shut down
195
alcohol effects on drunk driving
- increased probability of car accidents
- impaired reaction time and judgment
- increased aggression
196
alcohol effects: increased blood circulation
blood vessels dilated, feeling of warmth
197
alcohol effects: anti-diuretic hormone
ADH (anti-diuretic hormone) inhibited = increased urination and dehydration
198
alcohol effects: sleep
impairs REM sleep
199
alcohol effects: memory
blackouts/amnesia
200
alcohol effects on vestibular system
- alcohol makes blood less dense, which changes density of cupula compared to surrounding fluid
- sensation of movement triggers vestibular-ocular reflex
201
cupula
in semicircular canals (part of vestibular system in inner ear), senses movement
202
alcohol withdrawal: hangover
seen as a mini-withdrawal
203
alcohol withdrawal: chronic use
- can be fatal
- seizures, hallucinations, tremors, autonomic disruption
- treated using benzos because of cross-dependence
204
acute tolerance of alcohol
- aka tachyphylaxis
| - ascending and descending BAC
205
metabolic tolerance of alcohol
- increased expression of ADH
| - induction of liver enzymes of cytochrome P450 family
206
other types of alcohol tolerance
behavioral, pharmacodynamic, cross-tolerance with benzos/barbs
207
negative effects of chronic heavy alcohol use
- liver damage (~10-20%)
| - brain damage, including Korsakoff syndrome
208
fetal alcohol syndrome
- alcohol readily crosses placenta
- lower birth body weight
- craniofacial malformations
- neurological problems
- binge drinking and high BAC have been implicated in FAS
209
risks for alcoholism
- stress
- lifetime anxiety
- early-life stress
- increased novelty seeking
- family history of alcoholism
210
self-administration of alcohol in animals
- most animals will drink only a little alcohol
| - selective breeding --> populations that drink more alcohol or abstain completely
211
forms of barbiturates
- comes from barbituric acid (synthetic)
| - barbital and phenobarbital were first drugs to be marketed
212
barbiturate uses (overall)
- anxiolytics, hypnotics, and anticonvulsants
| - "truth serum"
213
medical use for barbiturates
- anesthesia
- sedation
- epilepsy
214
risks of barbiturates
significant addiction potential and overdose risk
215
drug that replaced barbs
benzos
216
retired uses of barbs
- sleep induction
- anxiety
- alcohol withdrawal (too dangerous)
217
DEA schedule for barbs
II, III, IV
218
side effects of barbs
- reduced REM sleep and slow wave sleep
- reduced cognitive function
- dangerous with alcohol
- tolerance --> dose escalation --> reduced margin of safety
- dependence and withdrawal (seizures)
219
barbiturate abuse
used recreationally to relieve anxiety, decrease inhibition
220
barbiturate effects at high doses
respiratory centers in the brainstem shut down, common means of suicide
221
use of benzodiazepines
- anxiolytics
- sedatives
- anticonvulsants
- treatment for alcohol withdrawal
- surgical sedation/amnesia
222
duration of action for benzos
varies for different benzos due to
- depot binding
- metabolic pathways (active vs inactive metabolites)
223
properties of nonbenzodiazepines
- similar benefits, side effects, and risks
| - different chemical structure from benzos
224
use for nonbenzos
sleep disorders
225
pharmacodynamic properties of nonbenzos
act at the binding site of GABAa receptors
226
medical uses of benzos
- schedule IV
- anxiety
- emotional stress
- relief from agitation and alcohol withdrawal
- sedation
- pre-surgery relaxation & anterograde amnesia
- anticonvulsant
- amnesia (roofies)
227
safety of benzos compared to barbs
- less metabolic tolerance
- lower dependence and abuse
- higher therapeutic index; do not affect respiratory centers in brain
- much harder to take a lethal overdose of benzos
228
reversal agent for benzos
Flumazenil, competitive antagonist for benzos
229
abuse of benzos
less liable to be abused by humans than barbs
230
dependence/withdrawal of benzos
- milder form of alcohol/barbiturate withdrawal symptoms
| - persistent emotional disturbances following withdrawal
231
other forms of abuse for benzos
Rohypnol (date rape drug)
232
DUI dangers of benzos
- sleep medications (Ambien) can leave people drowsy in the morning
- possibility of "sleep driving"
233
anxiolysis of barbs/benzos
- both are anxiolytic in animals and humans
234
pharmacodynamics of sedative-hypnotics
enhance chloride influx through GABAa receptors (ionotropic)
235
pharmacodynamics of barbs/benzos
unique binding sites on GABAa receptors
236
pharmacodynamics of alcohol
unknown mechanism at GABAa receptor
237
similarities of alcohol to barbs/benzos
- similar spectrum of behavioral effects
- similar increase in chloride currents
- cross-tolerance and cross-dependence
238
quaaludes
originally used as a hypnotic, sedative, or muscle relaxant
239
use of GHB
- decreased use now due to abuse potential
- subjective effects of GHB mostly resemble alcohol
- mild stimulant-like effects
- Xyrem for narcolepsy/cataplexy
240
abuse of GHB
club drug and date-rape drug
241
mechanism of action for GHB
acts as an agonist for GHB receptor and GABAb receptor (both GPCRs)
242
GABAb vs GHB receptor in response to GHB
GABAb receptor primarily involved in behavioral effects of GHB
243
GHB: GABAb knockout mice
do not display typical behavior or physiological effects to GHB
244
GHB: GHB receptors in mice
normal mice don't respond to a selective agonist for GHB receptor
245
GABA in the brain
- most important inhibitory neurotransmitter in the adult, vertebrate brain
- found throughout brain in high concentrations (many neurons and nuclei)
- important role in regulating excitation
246
GABA synthesis
GABA is formed from glutamate (immediate precursor) via enzyme glutamic acid decarboxylase (GAD)
247
VGAT stands for...
vesicular GABA transporter
248
GABA transporters
GAT-1, GAT-2, GAT-3 (on neurons and glia); transports GABA out of synapse
249
GABA metabolism/degradation
via the enzyme GABA amino-transferase (GABA-T)
250
GABAa receptors
- ionotropic
- ligand-gated Cl- channels
- 5 subunits (2 alpha, 2 beta, 1 gamma)
251
GABAb receptors
- metabotropic
- need two different subunits
- autoreceptor
252
GABA binding to GABAa
increased Cl- conductance --> hyperpolarization and IPSPs
253
mechanism of action for barbs/benzos
- act at different site of GABAa receptors
| - act at a different site than GABA
254
mechanism of action for all sedative-hypnotics
enhance chloride influx through GABAa receptors
255
benzo effects of GABA transmission
- cause GABAa channels to open more frequently
| - need GABA; benzos have no effect alone, benzos are positive allosteric modulators
256
barb effects of GABA transmission
- cause GABAa channels to stay open for longer durations
| - barbs have some direct agonist effects without GABA
257
benzo binding site
- discovered in 1977
| - benzo binding correlates with anxiolytic effects
258
benzo inverse agonists (beta-carbolines)
- beta-carbolines negatively modulate GABAa receptor
| - found in psychedelic drug ayahuasca
259
GABAa subunits: benzo behavioral effects
GABAa receptors with different subunits are differentially involved in various behavioral effects of benzos
260
alpha2 subunit: anxiolytic effects on benzos
anxiolytic effects require alpha2-conditioning GABAa receptors
261
alpha1 subunit: rewarding effects of benzos
- rewarding effects require alpha1-containing GABA receptors
| - increase firing of VTA dopamine neurons via disinhibition
262
low to moderate effects of alcohol
specific, acute effects
263
high doses of alcohol
nonspecific effects
264
acute effects of alcohol on glutamate mechanisms
- inhibits glutamate transmission
- reduces effectiveness of glutamate actions at NMDA receptor
- results in memory loss
265
chronic effects of alcohol on glutamate mechanisms
- upregulation of NMDA receptors
| - hyperexcitability during withdrawal
266
acute effects of alcohol on GABA mechanisms
increases GABA-induced Cl- influx at GABAa receptor
267
chronic effects of alcohol on GABA mechanisms
- reduces GABAa-mediated Cl- influx
| - hyperexcitability during withdrawal
268
acute effects of alcohol on DA mechanisms
- increases DA transmission
| - alcohol self-administration reduced, but not blocked, by DA antagonist or 6-OHDA lesions
269
chronic effects of alcohol on DA mechanisms
- reduction in DA transmission
| - withdrawal-induced negative affect and reduction in DA
270
acute effects of alcohol on opioid mechanisms
- increases endogenous opioids
| - Alcohol self-administration decreased by opioid antagonist or μ opioid receptor knockout
271
chronic effects of alcohol on opioids mechanisms
reduces opioid production
272
alcohol treatment: detoxification
benzodiazepine replacement
273
alcohol treatment: psychosocial
self-help groups
