Age-dependent morphine intake and cue-induced reinstatement, but not escalation in intake, by adolescent and adult male rats

Despite increasing rates of opioid abuse by human adolescents, few laboratory experiments address adolescent vulnerability to opiates. We examined intravenous morphine self-administration after adolescent- vs. adult-onset, followed by extinction and cue-induced reinstatement. Adolescent male Sprague–Dawley rats [postnatal day (P) 35 at start] and adults (P91) acquired lever pressing maintained by 0.375 mg/kg/infusion morphine on a fixed ratio one schedule of reinforcement. Subjects were subsequently divided into short or long daily access conditions (ShAcc, 1-h vs. LgAcc, 8-h; 18 sessions). After extinction, cue-induced reinstatement was recorded over 1 h. During the first six 1-h acquisition sessions and continuing throughout ShAcc conditions, adolescent-onset rats self-administered less morphine than adults, an effect commonly interpreted as higher drug sensitivity. In contrast under LgAcc conditions, escalation of morphine intake was similar across ages. Extinction of drug-seeking was similar across ages, although rats from LgAcc conditions pressed more than ShAcc conditions. Notably, cue-induced reinstatement was less robust in rats that began morphine self-administration during adolescence vs. adulthood. Although increased sensitivity of younger rats to morphine reinforcement under ShAcc conditions might help explain opioid abuse by human adolescents, lower rates of reinstatement in younger rats might suggest that adolescent development includes some protective factors that dampen the long-term impact of early drug intake.