Amphetamine treatment during the preweanling period produces enduring changes in striatal protein kinase A activity

The purpose of this study was to determine whether chronic exposure to amphetamine during the preweanling period causes enduring changes in behavioral and neuronal functioning. In two experiments rats were injected with saline or amphetamine (2.5 or 5.0 mg/kg) on postnatal days (PD) 11-15. Rats then received a challenge injection of saline or 2.5 mg/kg amphetamine on PD 23 or PD 90 and locomotor activity was measured. After behavioral assessment, rats were killed, and their dorsal striata and nucleus accumbens were dissected and later assayed for protein kinase A (PKA) activity. Interestingly, amphetamine treatment during the preweanling period produced an enduring decline in dorsal striatal and accumbal PKA activity that was still apparent in adulthood. These reductions in PKA activity were not related to the occurrence of locomotor sensitization, because rats did not exhibit a sensitized locomotor response when challenged with amphetamine at PD 23 or PD 90.