Repeated administration of amphetamine in animals induces persistent changes in dopamine (DA) functions and behaviour. These changes may be mediated by altered plasticity of the mesocorticolimbic DA system. We have previously reported changes in the content of axonal plasma membrane protein syntaxin-1 in the nucleus accumbens (NAc) of amphetamine-sensitized rats. In the present investigation, we investigated whether syntaxin-1 changes are derived from transcriptional events, i.e. mRNA changes, in the mesocorticolimbic DA regions of the brain. Behavioural sensitization was induced in adult Sprague-Dawley rats by repeated intermittent administration of d-amphetamine (1.5 mg/kg i.p. for 5 alternate days). The animals were sacrificed 24 h, 7 d or 14 d after the last injection and in-situ hybridization using oligonucleotide probes was employed to assess the expression of syntaxin-1A and -1B mRNAs. Results show that the expression of syntaxin-1B mRNA was significantly increased in the NAc shell (NAcS) region in the amphetamine-sensitized rats 14 d after the drug treatment compared to saline pretreated or untreated control animals No significant change in syntaxin-1B mRNA was observed in animals sacrificed 24 h or 7 d after the sensitizing regimen of amphetamine in any brain region analysed, namely NAcS, NAc core (NAcC), caudate putamen (CPu), ventral tegmental area (VTA) or medial prefrontal cortex (mPFC). Levels of syntaxin1A mRNA were not significantly different from controls in any brain region at any time-point. These results suggest that syntaxin-1 protein changes in amphetamine-sensitized rats may be due to increased syntaxin-1B gene expression within local neurons of the NAcS that may lead to altered exocytosis from these neurons during the expression of sensitized response.