Selective D1 or D2 dopamine receptor antagonists were used to investigate the transynaptic regulation of mRNAs coding for the opioid peptide, preprodynorphin, and the nuclear transcription factor, zif/268 after an acute cocaine binge. Rats were injected intraperitoneally with the D1 receptor antagonist, SCH 23390, or the D2 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 indicated that SCH 23390 blocked, whereas sulpiride augmented, cocaine-induced stereotypical behaviors. Striatal sections were hybridized with oligonucleotides coding for zif/268 and preprodynorphin. Quantitative image analysis of autoradiograms revealed that (1) SCH 23390 completely suppressed basal and cocaine binge-induced zif/268 mRNA in the striatal and cerebral cortical areas examined; (2) sulpiride enhanced basal levels of zif/268 mRNA in the medial caudate and dorsomedial shell of the nucleus accumbens; (3) sulpiride partially blocked cocaine binge-induced levels of zif/268 mRNA in the dorsal striatum but had no effect 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 preprodynorphin mRNA in the dorsal striatum.