Cocaine and methamphetamine differentially affect opioid peptide mRNA expression in the striatum

In general, administration of methamphetamine and cocaine alters preprodyno rphin and preproenkephalin mRNA levels in striatum. However, no study has d irectly compared the effects of these stimulants on opioid peptides in stri atum. This study used in situ hybridization to compare directly the effects of cocaine and methamphetamine on preprodynorphin and preproenkephalin mRN As in distinct striatal regions. Male Sprague-Dawley rats received a single administration of 15 mg/kg methamphetamine or 30 mg/kg cocaine and were ki lled 30 min or 3 h later. Methamphetamine and cocaine differentially affect ed preprodynorphin mRNA in striatum after 3 h. Densitometric analysis of fi lm autoradiograms revealed that cocaine, but not methamphetamine, significa ntly increased preprodynorphin. This effect was seen throughout rostral str iatum and dorsally in caudal striatum. However, specific analysis of "patch es" in which preprodynorphin expression is high revealed a significantly gr eater effect of methamphetamine versus cocaine. In contrast, both cocaine a nd methamphetamine had similar effects on preproenkephalin mRNA, decreasing levels after 30 min in rostral striatum and in the core of nucleus accumbe ns. These data suggest that methamphetamine and cocaine have distinct posts ynaptic consequences on striatal neurons.