Methamphetamine Exposure During the Preweanling Period Causes Prolonged Changes in Dorsal Striatal Protein Kinase A Activity, Dopamine D2-like Binding Sites, and Dopamine Content

Exposure to methamphetamine (METH) during the preweanling period produces few, if any, neurotoxic effects (using criteria established in adult rats), yet it has substantial long-term effects on a variety of behavioral measures (e.g., locomotor activity, acoustic startle response, and spatial learning). The purpose of the present study was to examine the long-term changes in dopaminergic functioning brought about by early METH exposure. Rats were injected with METH (10 mg/kg) or saline four times daily on postnatal days (PD) 11-20 and housed undisturbed until PD 90, at which time they were killed and their dorsal striata (i.e., caudate-putamen) were removed and frozen for assay. The ability of early METH exposure to alter protein kinase A (PKA) activity and dopamine (DA) D(2)-like binding sites, as well as DA and DOPAC content, were assessed. Results showed that METH exposure on PD 11-20 caused long-term reductions in all of the dopaminergic markers assayed. METH-induced reductions in DA content and D(2)-like receptors were observed. Some sex differences were apparent, as the METH-induced decreases in PKA activity and DOPAC content were more evident in male rats. In conclusion, preweanling METH exposure caused changes in DA markers that were still detectable at PD 90; however the magnitude of many of these effects (e.g., the reductions in DA and DOPAC levels) was substantially less than typically reported for rats treated with METH in adulthood. The ability of METH to cause long-term reductions in PKA activity may partially account for some of behavioral deficits exhibited by rats exposed to METH prior to weaning.