Several studies have shown that psychostimulants can induce differential immediate early gene and neuropeptide expression in the patch versus matrix compartments of dorsal striatum. The patch compartment contains a high density of mu opioid receptors and activation of these receptors may contribute to psychostimulant-induced gene expression in the patch versus matrix compartments of dorsal striatum. However, the contribution of mu opioid receptor activation to psychostimulant-induced changes in gene expression in the patch compartment of dorsal striatum has not been examined. The current study examined the role of mu opioid receptors in psychostimulant induction of preprodynorphin, c-fos and zif/268 messenger RNA expression in the patch versus matrix compartments of dorsal striatum. Male Sprague-Dawley rats were treated with the mu opioid receptor antagonist, clocinnamox (1 mg/kg, s.c.), 24 h prior to treatment with cocaine (30 mg/kg, i.p.) or methamphetamine (15 mg/kg, s.c.) and sacrificed 45 min or 3 h later. Mu opioid receptor antagonism blocked psychostimulant-induced preprodynorphin messenger RNA expression only in the rostral patch compartment, whereas psychostimulant-induced zif/268 messenger RNA expression in the patch and matrix compartments was attenuated throughout the dorsal striatum. Clocinnamox pretreatment had no effect on stimulant-induced increases in c-fos expression. These data suggest that mu opioid receptor activation plays a specific role in psychostimulant-induced preprodynorphin messenger RNA expression in the rostral patch compartment and zif/268 messenger RNA expression throughout dorsal striatum.