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 (0.4 mg/kg s.c.) significantly increased extracellular concentrations of dopamine and of dihydroxyphenylacetic acid (DOPAC) by 75-80% in nucleus accumbens of rats. Isoarecolone (3.2-32 mg/kg s.c.) had no significant effect on either dopamine or DOPAC levels in this brain region and neither drug affected extracellular levels of 5-hydroxy indole acetic acid. Both nicotine and isoarecolone induced head-bobbing behaviour. Pretreatment with ketanserin reduced nicotine-induced head-bobbing 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.
3,4-Dihydroxyphenylacetic Acid Animals