DOSE-DEPENDENT ALTERATION IN ZIF 268 AND PREPRODYNORPHIN MESSENGER-RNA EXPRESSION INDUCED BY AMPHETAMINE OR METHAMPHETAMINE IN RAT FOREBRAIN/

The dose-related effects of a single injection of D-amphetamine (AMPH) or methamphetamine (METH) on the mRNA expression of the immediate ear ly gene zif/268 and the opioid peptide preprodynorphin, in rat forebra in, were investigated with quantitative in situ hybridization histoche mistry 3 h after injection. Both drugs at equimolar doses (3.75, 7.5, 15 and 30 mu mol/kg) up-regulated zif/268 mRNA expression in cerebral cortex in a dose-dependent fashion. In the ''nose'' area of the sensor y cortex, all doses of METH, but not AMPH, induced a substantial, dose -dependent increase in zif/268 mRNA. Dose-dependent induction of zif/2 68 mRNA also occurred in caudoputamen after injection of AMPH at all d oses. However, dose-dependent increases in zif/268 mRNA in caudoputame n in METH-treated rats and in nucleus accumbens in AMPH-treated and ME TH-treated rats were seen only after the three lower doses. Injection of 30 mu mol/kg actually decreased zif/268 mRNA induction in these are as to or below that detected after 3.75 mu mol/kg. Preprodynorphin mRN A expression in the striatum was dose-dependently increased by either drug at all doses. These results demonstrate a clear dose-related resp onsiveness of zif/268 and preprodynorphin gene expression in cortical and/or striatal neurons that is positively correlated with a dose-depe ndent motor-stimulating effect of AMPH and METH. METH is a more potent psychostimulant than AMPH in eliciting behavioral and genomic activit y at equimolar doses, and METH elicits a qualitatively different patte rn of genomic activity in some forebrain regions, especially in the hi gher dose range.