Attenuated effects of experimenter-administered heroin in adolescent vs. adult male rats: physical withdrawal and locomotor sensitization

Abstract

Early onset of heroin use during adolescence might increase chances of later drug addiction. Prior work from our laboratory suggests, however, that adolescent male rats are actually less sensitive than adults to some enduring effects of heroin self-administration. In the present study, we tested two likely correlates of sensitivity to behavioral reinforcement in rats: physical withdrawal and locomotor sensitization. Adolescent (35days old at start) and adult (79days old) male Sprague-Dawley rats were administered escalating doses of heroin, increasing from 1.0 to 8.0mg/kg (i.p.) every 12h, across 13days. Somatic signs of spontaneous withdrawal were scored 12 and 24h after the last injection, and then every 24h for 5days; locomotion was recorded concurrently. Challenge injections of heroin (1mg/kg i.p.) were given at four points: as the first of the escalating doses (day 1), at days 7 and 13 during the escalating regimen, and after 12days of forced abstinence. Body mass and food intake were measured throughout experimentation. A heroin withdrawal syndrome was not observed among adolescents as it was among adults, including somatic signs as well as reduced locomotion, body mass, and food intake. On the other hand, heroin-induced locomotor sensitization did not differ across ages. Reduced withdrawal is consistent with the attenuated reinforcing effects of heroin among adolescent male rats that we reported previously. Thus, it is possible that adolescent rats could reveal important neuroprotective factors for use in treatment of heroin dependence.