Heroin self-administration and reinstatement of heroin-seeking in adolescent vs. adult male rats

Heroin abuse is prevalent among teenagers, and early onset drug use might predict long-term drug dependence. However, adolescent sensitivity to drug reinforcement has not been explored thoroughly in animal models. This study aimed to compare intravenous (i.v.) self-administration of heroin, as well as extinction and reinstatement of heroin-seeking, in adolescent vs. adult male rats. Adolescent (35 days old at start) and adult (86 days old at start) male Sprague-Dawley rats spontaneously acquired lever pressing maintained by i.v. heroin infusions. In experiment 1, self-administration was tested on a fixed ratio 1 schedule of reinforcement (0.05 and 0.025 mg/kg per infusion), followed by within-session extinction and reinstatement tests after 1 or 12 days of abstinence. In experiment 2, self-administration was tested on a progressive ratio schedule (0.0125-0.1 mg/kg per infusion), followed 12 days later by a single test of extinction responding in the presence of cues. In experiment 1, adolescent rats self-administered more heroin than adults. After 1 or 12 days of abstinence, adolescents exhibited less heroin-seeking than adults, although levels of heroin-seeking increased over abstinence period for both age groups. In experiment 2, adolescents and adults reached the same maximal response ratio (breakpoint), although adolescents earned more infusions when response requirements were low. For extinction responding in the presence of cues, heroin-seeking was similar across ages. Lower levels of heroin-seeking suggest that younger rats are less sensitive than adults to some residual effects of heroin intake.