Ontogeny of the adrenal response to (+)-methamphetamine in neonatal rats: the effect of prior drug exposure

We examined the ontogeny of the corticosterone response to (+)-methamphetamine in neonatal rats. In experiment-1, animals were injected with 10 mg/kg of (+)-methamphetamine or saline and plasma corticosterone levels were examined in separate groups 30 or 105 min later on postnatal day (P) 1, 3, 5, 7, 9, 11, 13, 15, 17, or 19. The adrenal response to methamphetamine was best described by a U-shaped function with the nadir of corticosterone release occurring between P7 and P13. Experiment-2 was similar except that the effect of four consecutive days of exposure to (+)-methamphetamine (four times daily at 2 h intervals with 10 mg/kg) was assessed with a single final dose early on the fifth day (i.e. P1-5, 3-7, 5-9, 7-11, 9-13, 11-15, 13-17, 15-19). The 30 min corticosterone response after multiple methamphetamine doses was augmented compared to single exposures, with the exception of the two earliest dosing intervals ending on P5 and P7, where the responses were lower. In addition, at 105 min, the levels of corticosterone were attenuated relative to a single drug administration. With the exception of animals receiving methamphetamine from P15 to P19, thymus weights were unaffected. The data demonstrate that (+)-methamphetamine is a robust activator of corticosterone release in developing animals and this release is extensively modified by age and previous drug exposure.