Abstinence & Incubation of Drug Seeking

Question 1

abstinence procedure

Answer 1

abstinence achieved through extinction training in relapse reinstatement. humans do not go through extinction. EXPERIMENT: cocaine trained rats self administer. put through abstinence (put in different environment) and then brought back to drug environment. put through drug seeking test but they dont get the drug. response is very high. injected with GABA agonist, inhibition of dmPFC does not decrease drug seeking. inhibitor of basolateral amygdala does not decrease drug seeking response. lower drug seeking seen in dorsal striatum when injected with GABA agonist.

BLA critical for cue induced reinstatement. shut down PFC, significant decrease in reinstatement.

context induced = train animals in 1 environment, extinguish cocaine seeking in another environment, bring back to initial environment = there is reinstatement of drug seeking behaviour. block context dependent reinstatement by injecting GABA agonist.

Question 2

incubation of drug seeking : heroin

Answer 2

heroin self administration, different groups of rats, after training left them for different periods of forced abstinence and then started extinction. found that animals that had 1 day of forced abstinence has a relatively low level of response of the first session. animals really interested were the ones with 6,12,25 days of forced abstinence. too long of a period, 66 days, dont show much interest. went through extinction sessions until all groups showed low levels of response. exposed to foot shock. found that animals with 1 day of withdrawal didnt even show reinstatement, animals with longer periods of withdrawal showed higher responses than baseline. longer periods of abstinence actually results in stronger craving (for cue and stress)

Question 3

incubation of drug seeking : cocaine

Answer 3

trained rats to self administer cocaine, different periods of forced abstinence. go through extinction sessions until they have low responses. the longer the abstinence period, the stronger the craving. extinction was without the cues. went through cue induced reinstatement test. animals with 1 day of withdrawal show little reinstatement. longer abstinence periods show higher craving/reinstatement from cues.

Question 4

incubation of drug seeking: sucrose

Answer 4

self administer sucrose. different abstinence periods from sucrose. bring them back to environment and see reinstatement. cue induced reinstatement. highest response for the rats with 1 month of abstinence. incubation = increase over time of the craving.

Question 5

incubation of drug seeking: smoking

Answer 5

recruited smokers, after different periods of abstinence, exposed to cue induced reinstatement, assess their craving. after 7 days, little craving even repulsion. after 14 days, higher cravings. 35 days = stronger craving. the longer the abstinence, the craving induced by cues is stronger.

Question 6

incubation of drug seeking : alcohol

Answer 6

recruited alcohol users, after different periods of abstinence, exposed to cue induced reinstatement, assess their alcohol craving. 7 days of abstinence = little craving, some repulsion. as abstinence period gets longer, show stronger cue induced craving.

Question 7

incubation of drug seeking : brain adaptations

Answer 7

cocaine trained rats after 1,30,90 abstinent days and still see this incubation of cocaine seeking (cue induced). looked for changes in levels of neurotropic factors in different areas of the brain. identified changes in amygdala, NAc, VTA (higher levels of BDNF). tested the effects of injecting BDNF into brain areas such as VTA = can induce an increase in cocaine craving. BDNF = involved in development of craving over time. can see Glu receptor adaptation. trained animals to self administer cocaine, had 1, 45 days of withdrawal. demonstrated cocaine incubation over days. ran an analysis of Glu receptors. only change seen was an increase in GluA1 (permeable to calcium) receptor = more AMPA with GluA1 in NAc. ran the experiment again, injected Naspm (antagonist for receptor) - significantly reduced craving when targeted this receptor. calcium increase drives craving behaviour. critical factor in heroin trained rats = GDNF. same study for heroin trained rats. specific mechanisms of incubation generalized to cocaine and heroin.

Question 8

chronic food restriction

Answer 8

trained rats to self administer heroin. after 2 weeks of abstinence, put on food restriction, bring them back to drug environment to seek heroin. see an increase in response but the hungry animals press significantly more (600x). being hungry drives robust craving.