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 a gonists amphetamine and methamphetamine on behavior and messenger RNA expression were evaluated. Expression of c-fos, a member of the leucin e zipper family, zif/268 (NGFI-A, egr1 and Krox-24), a member of the z inc finger family, and the opioid peptide, preprodynorphin, was invest igated in various regions of rat forebrain with quantitative in situ h ybridization histochemistry 1, 2, 3, 6 or 30 h after injection. Behavi oral observations indicated that a qualitatively different behavioral syndrome was induced following methamphetamine (15 mg/kg, i.p.) as com pared with that observed after amphetamine (5 mg/kg, i.p.). Similarly, methamphetamine amine induced a different pattern of c-fos and zif/26 8 messenger RNA induction in sensory/motor cortex, dorsal striatum (ca udatoputamen) and ventral striatum (nucleus accumbens) than did amphet amine. The increase in c-fos messenger RNA expression peaked at 1 h an d returned to basal levels in all regions by 3 h. In contrast, the inc rease 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 messeng er RNA levels peaked at 1 h and declined gradually to basal levels by 6 h. Interestingly, methamphetamine caused an actual suppression of zi f/268 gene expression (> 50%) in both caudatoputamen and nucleus accum bens 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 th at 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 an d striatum by amphetamines over time. These data implicate immediate e arly gene and preprodynorphin gene expression in the differential resp onse of medium spiny striatal neurons to methamphetamine and amphetami ne.