Ontogeny of the enhanced behavioral response to amphetamine in amphetamine-pretreated rats

Repeated administration of amphetamine to adult rats results in enhanced behavioral responses to subsequent amphetamine exposure. These experiments were designed to determine the earliest age at which behavioral sensitization to amphetamine could be detected. Rats from both sexes (n = 6-8/group) at ages of 1, 7, 21 or 49 postnatal days (PNDs) were injected with either d-amphetamine sulfate (5 mg/kg) or saline, SC, twice daily for 5 consecutive days. Stereotyped behavior and locomotor activity responses to a challenge dose of d-amphetamine (2.5 mg/kg), or saline, IP, were assessed for a total of 90 min, 15 days after the last dose of pretreatment. Amphetamine-induced stereotyped behavior was significantly enhanced only when amphetamine pretreatment was initiated at PND 49, but not at the earlier ages of PND 1, 7 or 21. There was no apparent sex difference in this effect. Correspondingly, amphetamine-induced locomotor activity was reduced in both sexes of the same age group (PND 49), but not in groups pretreated earlier, when compared to the saline-pretreated rats. These results suggest that amphetamine sensitization may be a late-developing effect, one which occurs sometime after the 3rd week of postnatal life.