Extinction and drug‐induced reinstatement of cocaine seeking following self‐administration or conditioned place preference in adolescent and adult rats

Abstract

Adolescence marks a particularly vulnerable period to developing substance use disorders, and people who start using drugs in adolescence are more likely to relapse. A limited number of studies have investigated age difference in relapse following reexposure to the drug after a period of abstinence. Using a cocaine self-administration paradigm, we showed no age difference in acquisition or extinction of self-administration. Interestingly, adolescent rats displayed impaired cocaine-primed reinstatement of cocaine seeking. Using the same dose as that self-administered in the first experiment, we then investigated age differences in acquisition and extinction of conditioned place preference, as well as locomotor sensitization. While there were no differences in locomotor activity or acquisition of preference, adolescents failed to extinguish their preference, even when the number of extinction sessions was doubled from what adults received. Taken together, these results suggest that while cocaine has similar rewarding and reinforcing effects regardless of age, adolescents may attribute stronger salience to the drug-associated context. In addition, re-exposure to cocaine itself may not be a strong relapse trigger in adolescence. Overall, these findings suggest that we should focus more on alleviating drug-context salience compared to re-exposure to substance in order to reduce relapse of drug seeking in adolescents.

Incubation of Oxycodone Craving Following Adult-Onset and Adolescent-Onset Oxycodone Self-Administration in Male Rats

“…However, it is unknown whether adolescent-onset oxycodone self-administration impacts relapse behavior in the adulthood after abstinence. Note that previous studies on the effect of adolescent-onset drug self-administration on drug seeking yielded mixed results (Doherty et al, 2009;Frantz, 2009, 2017;Doherty and Frantz, 2012;Wong and Marinelli, 2016;Madsen et al, 2017;Cho et al, 2020;Guerin et al, 2021) (see details in Discussion), but the majority of the studies do not support the notion that adolescent-onset drug self-administration promotes relapse behavior in adulthood. Here, we aimed to compare incubation of oxycodone craving following adolescent-onset and adult-onset oxycodone selfadministration.…”

Insular cortex dopamine 1 and 2 receptors in methamphetamine conditioned place preference and aversion: Age and sex differences

“…Further, protein inhibition of insula after CPP recall or extinction has been shown to prevent CPP expression for upto 24 days [42]. Thus, ageand sex-specific assessment of insula's role in CPP/CPA following extinction appears warranted considering extinction deficits reliably observed in adolescent rodents and humans [75][76][77][78][79][80].…”

Mitragynine, a primary constituent of kratom reinstates morphine-seeking behaviour in rats

“…Drug relapse and craving are often provoked by acute exposure to the self-administered drug or related drugs, drug-associated cues or contexts, or specific stressors (Drummond et al, 2000;Guerin et al, 2021). The 'extinction-reinstatement model', which typically involves intravenous self-administration and conditioned place-preference (CPP) paradigms, represents the most common experimental protocols to study drug-seeking and relapse-like behaviour in animals.…”