withdrawal and tolerance
experiment to test nicotine withdrawal effects on cognitive performance?
2-back task - attention and memory nonsmokers better than smokers abstinence increased cognitive impairment
DSM criteria for substance use disorder?
3/7 needed tolerance withdrawal binging failure to quit/control use despite wanting to preoccupation with drug use - large amount time/effort in activities to obtain the drug reduction in non-drug activities in favour of drug continued use despite knowledge of bad shit
what is tolerance
a need to increase drug dose to achieve intoxication or desired effect, or a diminished effect with the same dose (as a result of down-regulation and desensitisation)
what are characteristics of cocaine/amphetamine withdrawal syndrome?
act on dopamine and serotonin (motivation, euphoria, confidence) therefore, loss of motivation, depression, and anxiety decrease in activity in mesolimbic dopamine neurons
what are characteristics of cannabis withdrawal syndrome?
anger, anxiety, sleep disturbance peak 1 week after abstinence, last about 27 days
experiments showing reduced dopamine activity in cocaine/amphetamine withdrawal?
cocaine: rats idk 49% reduction in dopamine cell activity 1.39 to 0.81 per track (I don't know what this means) meth: brain imaging less activity at one month abstinence than healthy controls more activity at 14 months abstinence less recovery if used for longer
how did Siegal explain relapse due to exposure to drug use cues?
conditioned tolerance ie cues in environment (CS) elicit b process (CR) that opposes drug process (immediately after ingestion) compensatory process grows over time -> conditioned exposure to these cues after recovery makes withdrawal state
what is receptor desensitisation and down-regulation and who do they occur?
desensitisation: number of receptors constant but ion channels become insensitive so that binding stops having an effect down-regulation: decrease in number of receptors -> neurotransmitters have less effect protect the cell from under or overstimulation which can lead to cell death (if drug acts on inhibitory, under fire, if on excitatory, overfire) results in tolerance
how does down-regulation and desensitisation relate to withdrawal?
down-regulation and desensitisation make your brain sweet when you're using the drug chronically if you stop using the drug, the neurotransmitter systems where it binded now under fire heaps. - experience opposite effects of the drug eg alcohol relaxation and euphoria becomes over-excitation and dysphoria
how does Wilker explain relapses when the person has gone through withdrawal?
environmental cues predict withdrawal (CS) elicit withdrawal state (CR)
what is withdrawal
having experienced characteristics of the withdrawal syndrome -> ailments following abstinence from drug use, or drug use to relieve or avoid the withdrawal syndrome
what are characteristics of nicotine withdrawal syndrome?
impaired cognition, depression, anxiety
why can sudden alcohol withdrawal be life-threatening?
increased glutamate and decreased GABA = overexcitation -> neurotoxic
Charles O'Brien experiment to show conditioned withdrawal state?
opiate addicts trial 1-3: injected with saline trial 4-18: injected with naloxone - produce withdrawal symptoms - paired with odour and sound trial 19-20: injected with saline paired with odour and sound in test trials showed conditioned withdrawal symptoms not present in trials 1-3
what are characteristics of opiate withdrawal syndrome?
pain, dysphoria, loss of motivation peaks at 2 days abstinence long time to abate persistent depression -> irreversible desensitisation/down-regulation
Siegal experiment to show conditioned tolerance to drug cues?
rats given alternating heroin and saline in distinct rooms dose increased over time on final day given mad dose - half in heroin room, half in saline room 1/3 in heroin room died 2/3 in saline room died -> cues elicit conditioned compensatory response
how is tolerance represented on dose-response function?
shift to the right ie more drug required for same effect (or same dose gives smaller effect) also maximum effect smaller bc of down-regulation and desensitisation
what is Wilker's theory of conditioned withdrawal?
withdrawal promotes relapse negative reinforcement: drug use to avoid withdrawal addiction driven by withdrawal avoidance