A SINGLE INJECTION OF AMPHETAMINE OR METHAMPHETAMINE INDUCES DYNAMIC ALTERATIONS IN C-FOS, ZIF/268 AND PREPRODYNORPHIN MESSENGER-RNA EXPRESSION IN RAT FOREBRAIN

In this study, the effects of a single dose of the indirect dopamine agonists amphetamine and methamphetamine on behavior and messenger RNA expression were evaluated. Expression of c-fos, a member of the leucine zipper family, zif/268 (NGFI-A, egr1 and Krox-24), a member of the zinc finger family, and the opioid peptide, preprodynorphin, was investigated in various regions of rat forebrain with quantitative in situ hybridization histochemistry 1, 2, 3, 6 or 30 h after injection. Behavioral observations indicated that a qualitatively different behavioral syndrome was induced following methamphetamine (15 mg/kg, i.p.) as compared with that observed after amphetamine (5 mg/kg, i.p.). Similarly, methamphetamine amine induced a different pattern of c-fos and zif/268 messenger RNA induction in sensory/motor cortex, dorsal striatum (caudatoputamen) and ventral striatum (nucleus accumbens) than did amphetamine. The increase in c-fos messenger RNA expression peaked at 1 h and returned to basal levels in all regions by 3 h. In contrast, the increase in zif/268 messenger RNA expression in the cortical regions was equally strong at 1 and 2 h, gradually returning to basal levels by 6 h after either drug. However, in the striatal regions, zif/268 messenger RNA levels peaked at 1 h and declined gradually to basal levels by 6 h. Interestingly, methamphetamine caused an actual suppression of zif/268 gene expression (> 50%) in both caudatoputamen and nucleus accumbens at 3 h. Preprodynorphin messenger RNA expression was increased in a patchy motif in the caudatoputamen and nucleus accumbens beginning at 2 h and returning to basal levels by 30 h after injection of either drug. This study, together with our recently published observation that preprodynorphin messenger RNA is induced in the caudate 3, 6 and 18 h after amphetamine or methamphetamine injection, provides a detailed dynamic description of the differential modulation of c-fos, zif/268 and preprodynorphin messenger RNA expression in the cerebral cortex and striatum by amphetamines over time. These data implicate immediate early gene and preprodynorphin gene expression in the differential response of medium spiny striatal neurons to methamphetamine and amphetamine.