The effects of D1 or D2 dopamine receptor blockade on zif/268 and preprodynorphin gene expression in rat forebrain following a short-term cocaine binge.

Abstract

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.