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

Abstract

Lower levels of heroin-seeking suggest that younger rats are less sensitive than adults to some residual effects of heroin intake.

A Role For The Prefrontal Cortex In Heroin-Seeking After Forced Abstinence By Adult Male Rats But Not Adolescents

“…Moreover, when the heroin dose was reduced by half, the number of infusions earned almost doubled, confirming that heroin reinforced lever-pressing. Although no age differences in the number of heroin infusions per session were observed in the present experiment, we reported slightly higher rates of heroin self-administration among adolescents compared with adults in a previous experiment (Doherty and Frantz, 2012a). Inconsistent patterns of self-administration have prompted us to question the reliability of age differences in the acutely reinforcing effects of opiates in the selfadministration procedure (Doherty and Frantz, 2012a).…”

“…Resolution between studies like ours demonstrating adolescent resistance to drug effects vs those demonstrating heightened drug sensitivity among adolescents may relate to the duration of drug exposure (eg, whether it ceases during adolescence or continues into adulthood), the intensity of drug exposure (eg, drug doses), and/or the parameters for testing drug effects. For example, we observed similar rates of reinstatement among adolescent-and adult-onset groups when both context and cues were renewed simultaneously (Doherty and Frantz, 2012a). Also, extinction of a cocaineconditioned place preference occurred at the same rate in adolescent and adult rats when explicit extinction procedures were used (Brenhouse et al, 2010), and the age-dependent effects of cocaine self-administration on cognition vary by which brain region mediates the cognitive task (Kerstetter and Kantak, 2007;Harvey et al, 2009).…”

“…What has remained consistent across our studies of heroin, morphine, and cocaine self-administration, however, is that male rats that initiate drug self-administration during adolescence exhibit attenuated drug-seeking after forced abstinence compared with rats that initiate selfadministration during adulthood (Doherty et al, 2009;Li and Frantz, 2009;Doherty and Frantz, 2012a). Our studies reveal attenuated responsivity among younger rats on measures of extinction responding in the absence of discrete drug-paired cues (as in the present study), and cueinduced reinstatement after extinction (see references above).…”

“…drug self-administration can be measured as reinstatement of lever-pressing triggered by contextual cues associated with the drug-taking environment (context-induced), discrete drug-paired cues (cueinduced), or reexposure to the drug itself (drug-primed; reviewed in Shaham et al, 2003). Despite reports suggesting that adolescence is a period of heightened vulnerability to drugs (eg, Spear (2000) and Crews et al (2007) for reviews), we have found that male rats that self-administered heroin, morphine, or cocaine as adolescents exhibit attenuated cue-induced reinstatement of drug-seeking after forced abstinence, compared with rats that self-administered in adulthood (Doherty et al, 2009;Li and Frantz, 2009;Doherty and Frantz, 2012a). This result was independently replicated with cocaine-seeking (Anker and Carroll, 2010).…”

“…Infusions were signaled by a compound stimulus (cue light above active lever, 5-s burst of white noise, house light off). The infusion volume and duration were adjusted daily based on individual body weight (see Doherty and Frantz (2012a) for details).…”