THE EFFECTS OF D-1 OR D-2 DOPAMINE-RECEPTOR BLOCKADE ON ZIF 268 AND PREPRODYNORPHIN GENE-EXPRESSION IN RAT FOREBRAIN FOLLOWING A SHORT-TERMCOCAINE BINGE/

Selective D-1 or D-2 dopamine receptor antagonists were used to invest igate the transynaptic regulation of mRNAs coding for the opioid pepti de, preprodynorphin, and the nuclear transcription factor, zif/268 aft er an acute cocaine binge. Rats were injected intraperitoneally with t he D-1 receptor antagonist, SCH 23390, or the D-2 receptor antagonist, sulpiride, 30 min prior to 3 hourly injections of saline or 20 mg/kg cocaine and killed 1 h after the final injection. Behavioral ratings i ndicated that SCH 23390 blocked, whereas sulpiride augmented, cocaine- induced stereotypical behaviors. Striatal sections were hybridized wit h oligonucleotides coding for zif/268 and preprodynorphin. Quantitativ e image analysis of autoradiograms revealed that (1) SCH 23390 complet ely suppressed basal and cocaine binge-induced zif/268 mRNA in the str iatal and cerebral cortical areas examined; (2) sulpiride enhanced bas al levels of zif/268 mRNA in the medial caudate and dorsomedial shell of the nucleus accumbens; (3) sulpiride partially blocked cocaine bing e-induced levels of zif/268 mRNA in the dorsal striatum but had no eff ect in sensory cortex; (4) SCH 23390, but not sulpiride, significantly reduced the constitutive expression of preprodynorphin mRNA; and (5) SCH 23390 and sulpiride blocked cocaine binge-induced expression of pr eprodynorphin mRNA in the dorsal striatum.