the nicotinic receptor agonists nicotine and isoarecolone differ in their effects on dopamine release in the nucleus accumbens this study compared the effect of the nicotinic receptor agonists nicotine and isoarecolone on the mesolimbic dopamine system of the rat using in vivo microdialysis previous studies showed that nicotine but not isoarecolone produced a locomotor activating effect and that this was probably mediated by increased concentrations of dopamine in the nucleus accumbens nicotine 04 mgkg sc significantly increased extracellular concentrations of dopamine and of dihydroxyphenylacetic acid dopac by 7580 in nucleus accumbens of rats isoarecolone 3232 mgkg sc had no significant effect on either dopamine or dopac levels in this brain region and neither drug affected extracellular levels of 5hydroxy indole acetic acid both nicotine and isoarecolone induced headbobbing behaviour pretreatment with ketanserin reduced nicotineinduced headbobbing suggesting a serotonergic mechanism in conclusion the absence of locomotor activation after administration of isoarecolone may be related to its failure to activate the mesolimbic dopamine system