DIFFERENTIAL-EFFECTS OF D-1 AND D-2 DOPAMINE-RECEPTOR ANTAGONISTS ON ACUTE AMPHETAMINE-INDUCED OR METHAMPHETAMINE-INDUCED UP-REGULATION OF ZIF/268 MESSENGER-RNA EXPRESSION IN RAT FOREBRAIN

This study investigated the hypothesis that D-1 and D-2 dopamine receptors interact to regulate the expression of zif/268 mRNA in rat forebrain after an acute injection of amphetamine or methamphetamine. Forty-five minutes and 3 h after a single injection of amphetamine (4 mg/kg i.p.) or methamphetamine (4 mg/kg i.p.), the mRNA expression of zif/268 in dorsal striatum and sensorimotor cortex was increased, as revealed by quantitative in situ hybridization histochemistry. Induction was more intense in striatal patches at 45 min than at 3 h, when a more homogeneous pattern of zif/268 mRNA induction was observed. SCH 23390, a selective D-1 receptor antagonist, suppressed, and eticlopride, a D-2 receptor antagonist, elevated, constitutive zif/268 mRNA levels in the striatum, but neither antagonist had a significant effect on the constitutive expression of zif/268 in sensorimotor cortex. Pretreatment with SCH 23390 completely blocked the stimulant-induced zif/268 expression in striatum and partially blocked the stimulant-induced zif/268 expression in cortex. Pretreatment with eticlopride augmented zif/268 mRNA expression in patch and matrix compartments of dorsal and ventral striatum 45 min after amphetamine or methamphetamine injection. However, at 3 h, eticlopride completely blocked amphetamine- and methamphetamine-stimulated zif/268 mRNA in dorsomedial, but not dorsolateral, striatum, in addition, eticlopride partially blocked cortical zif/268 induction by both amphetamines. Both antagonists prevented stimulant-induced hyperlocomotion and stereotypies. These results demonstrate that D-1 and D-2 receptors in mesolimbic/mesostriatal pathways both regulate amphetamine- and methamphetamine-stimulated behaviors and zif/268 mRNA expression. Furthermore, the effect of D-2 receptor blockade on zif/268 expression was found to be contingent on the time interval investigated after psychostimulant administration.