Differential effects of cocaine and methamphetamine on neurotensin/neuromedin N and preprotachykinin messenger RNA expression in unique regions of the striatum.

This study employed in situ hybridization to directly compare the effects of cocaine and methamphetamine on neurotensin/neuromedin N and preprotachykinin messenger RNAs in distinct striatal regions. Male, Sprague-Dawley rats received a single administration of 15mg/kg methamphetamine (s.c.) or 30mg/kg cocaine (i.p.) and were killed 30min or 3h later. Methamphetamine and cocaine produced significant increases in preprotachykinin messenger RNA in the striatum after 3h, but often in different subregions. Both drugs produced similar effects on preprotachykinin messenger RNA in the rostral striatum. However, methamphetamine produced significant increases in all regions of the caudal striatum, whereas cocaine-induced preprotachykinin messenger RNA expression was limited to dorsal regions of this striatal area. Methamphetamine also produced a significant increase in preprotachykinin messenger RNA in the caudal striatum after 30min, whereas cocaine had no significant effect on preprotachykinin messenger RNA at this early time-point. The pattern of changes in neurotensin/neuromedin N messenger RNA caused by methamphetamine and cocaine after 3h was even more distinct. Cocaine produced significant increases in neurotensin/neuromedin N messenger RNA in all regions of the rostral striatum, whereas methamphetamine had no effect in these areas. Furthermore, in more caudal sections, cocaine predominantly affected neurotensin/neuromedin N expression in dorsal aspects of the striatum, whereas methamphetamine significantly increased neurotensin/neuromedin N messenger RNA in all regions. There was much less effect of either drug on neuropeptide expression in the nucleus accumbens. The only significant effect was an increase in neurotensin/neuromedin N messenger RNA in the core region 3h after methamphetamine administration. These results indicate that methamphetamine and cocaine increase preprotachykinin and neurotensin/neuromedin N messenger RNAs in distinct regions of the striatum. The ability of methamphetamine and cocaine to alter neuropeptide messenger RNA expression in unique regions of the striatum may be important for the long-term effects of these drugs, such as sensitization, since the striatum is not homogeneous in its connections and function.