Heightened locomotor-activating effects of amphetamine administered into the nucleus accumbens in adolescent rats

There is a shift in sensitivity to systemically administered psychostimulants in adolescence, as evidenced by less amphetamine-induced locomotor activity in adolescent compared to adult rodents. Locomotor activating effects of amphetamine are dependent on drug actions in the core of the nucleus accumbens (NAc), but the contribution of this region to age differences in amphetamine sensitivity has not been studied directly. In the present study, we investigated the development of the NAc using targeted injections of amphetamine (0, 3, or 6 μg/side) directly into the NAc core in early (postnatal day 30; P30) or late (P45) adolescence, or in adulthood (P75). Locomotor activity was recorded during two 1 h sessions, 48 h apart. Amphetamine increased locomotor activity at all ages. P45 rats were more active than adults only at the 3 μg/side dose, but this difference was not significant when baseline activity was taken into account. In contrast, P30 rats were more active than adults at the 6 μg/side dose, indicating that the magnitude of the locomotor response is highest in early adolescence. Results of the present study are the first to directly show a developmental difference in the sensitivity of the NAc to amphetamine under conditions in which the influence of pharmacokinetic factors and regulatory brain regions is minimized.

► Conducted first study comparing age differences to intra-accumbens amphetamine. ► Dose-dependent age differences were found in amphetamine-induced activity. ► Pre- and post-pubertal adolescent rats were more active than adult rats. ► Indicates that nucleus accumbens is more sensitive to amphetamine in adolescence. ► Findings are consistent with increased risk for addiction in adolescence.