Amphetamine sensitization in reproductively experienced female rats

Recent studies have supported the hypothesis that pregnancy and parturition are associated with altered sensitivity of brain dopamine systems. An increased behavioral sensitivity to a direct-acting D1/D2 receptor agonist (apomorphine) has also been observed several weeks after lactation, suggesting that these adaptations are long-lasting. To further characterize this phenomenon, the effects of reproductive experience on behavioral sensitization to an indirect-acting dopamine agonist (amphetamine) in female rats were studied. In two separate experiments, nulliparous and primiparous (12-16 weeks post-weaning) female rats were pretreated with amphetamine (1.0 or 5.0mg/kg) or vehicle (saline) once daily for 5 consecutive days. After 10 days of withdrawal, all animals were challenged with a low dose of amphetamine (25% of pretreatment dose). Locomotor activity was measured following each drug or vehicle administration. Locomotor sensitization to amphetamine challenge was observed in all animals pretreated with 1mg/kg, regardless of reproductive experience. In contrast, primiparous animals pretreated with 5mg/kg amphetamine displayed a significantly larger locomotor response to the challenge compared to nulliparous controls. The findings indicate enhanced behavioral sensitization to amphetamine in reproductively experienced rats, and confirm previous reports of lasting adaptations of dopamine systems following pregnancy and lactation.