Relapse Reinstatement Flashcards
triggering factors
re-exposure to drug, re-exposure to stimuli associated with drug (incentive sensitization) , stress, withdrawal (conditioned withdrawal). EXPERIMENT: subjects were cocaine users. exposed them to all kinds of conditions such as cues, let them consume a little bit of it too, and scored their craving. craving before cue is a score of 45 then once they were exposed to cue, score goes up. once they take cocaine, craving also goes up. can study relapse through stress induced relapse.
reinstatement model and examples
reinstatement procedure the most common to study relapse. EXPERIMENT: trained animals to self administer cocaine or heroin. then drug seeking was extinguished then injected a single injection of cocaine or heroin to respective groups. animals allowed to press lever but do not get drug by pressing lever during test. test is usually done under extinction conditions. when exposed to drug, they increase the number of responses even though they had long training under extinction. this is priming induced relapse. another experiment using fixed ratio. animals learn how to self administer heroin. animals were responding quite a lot then started extinction process. extinction is done without any cues - only get the lever. on test day, reintroduce the cues, triggers reinstatement, animals go back to press lever even though they only get the cues. not the drug. this is cue induced reinstatement. experiment showing stress induced reinstatement. most common stress is electrical foot shock. animals trained to self administer heroin. one group got priming with heroin - animals showed priming induced reinstatement. injected with heroin right before test. other group exposed to foot shock stress just before test - effect even stronger. induces craving and the responses increase. one group exposed to priming and the other to stress = stress works better than priming. another experiment showing stress induced reinstatement uses food deprivation. 21 hours was effective in reinstating heroin seeking. they are not getting drug during test, this is pure craving (one of the advantages of doing this test). unable to show withdrawal induced reinstatement.
reinstatement model and CPP
induce morphine CPP. inject morphine in one place and saline in another environment and then extinguish place preference. animals don’t forget it. prime them before a test (infusion of morphine), put them in middle, you get the animals developing a conditioned morphine place preference. this is priming induced morphine CPP. can also do stress induced morphine CPP. use a forced swim stress. extinguish the place preference by dropping them in a bucket of water before the test. now show preference for morphine environment.
reinstatement model mechanisms : priming
brain areas involved are DA, Glu systems in the VTA, NAc, mPFC. self administered heroin, went through extinction, responses decreased due to extinction, primed with heroin injection before test. priming with saline doesnt show an effect. priming with heroin shows reinstatement. injected systemically naltrexone. naltrexone + heroin blocks reinstatement. tested effects of 3 DA receptor antagonists. D1 antagonist: at lower doses does not block reinstatement but at higher doses does. D2 antagonist: at low dose blocked reinstatement. nonspecific DA antagonist = completely blocked priming induced reinstatement. another experiment: injected with cocaine, extinction, priming with single dose of cocaine. increased responses showing priming induced reinstatement. injected DA antagonist into specific areas = dPFC completely blocked priming induced reinstatement, NAc saw no effects, VP (ventral pallidum) no effect. DA in dPFC important in priming induced reinstatement. injected solution of GABA agonists into VTA and primed with cocaine and saw no priming induced reinstatement. shut down VTA but injected DA in PFC and see priming induced reinstatement. anything that increases DA in dPFC will show priming induced reinstatement, directly increasing DA in PFC will increase cocaine seeking.
reinstatement model mechanisms : cue
brain areas involved are the DA (D1) systems in the basolateral amygdala, NAc, mPFC. animals self administer, go through extinction process, exposed to cue. see cue induced reinstatement in BLA (basolateral amygdala) after (tetrodotoxin) TTX injection when exposed to cocaine. see cue induced reinstatement in NAc after TTX injection when exposed to tone/light.
reinstatement model mechanisms : stress
brain areas involved : CRF, NE, DA systems in bed nucleus of stria terminalis (BNST) and amygdala. footshock releases CRF in VTA. animals become more responsive to stress. block CRF = block behaviours, no stress induced reinstatement, no increase in DA and Glu. CRF is necessary to see an increase only in cocaine trained rats. CRF drives increase in Glu and DA. blocking Glu receptors by an antagonist directly into VTA = blocks stress induced reinstatement, exposure to foot shock results in increase of Glu. block Glu receptors, block increase in DA. foot shock causes increase in CRF in all animals - in cocaine trained animals, this increase in CRF drives the increase of Glu and this increase in Glu drives the increase of DA. CRF is the driving force for stress induced reinstatement. trained animals to self administer cocaine, extinction, inject CRF directly. infused CRF through microdialysis probe directly into VTA = get reinstatement of cocaine seeking - increase in cocaine seeking can be blocked if given CRF receptor antagonist. infused CRF directly into VTA, got reinstatement, then blocked it with acid - showing if you block Glu using glutamate receptor antagonist you block the effect of CRF infusion on reinstatement. after 1,7,21 days of withdrawal, CRF injected into VTA led to Glu increase = sensitivity to CRF lasts a long time even without cocaine. when you infuse CRF, get an increase in Glu, this increase in Glu can be blocked by CRF receptor antagonist to show that this increase in Glu release is driven by increase of CRF. know that stress drives this increase of CRF but only in cocaine trained rats. Norepinephrine drives CRF which drives reinstatement.
