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 r at using in vivo microdialysis. Previous studies showed that (-)-nicot ine but not isoarecolone produced a locomotor activating effect, and t hat this was probably mediated by increased concentrations of dopamine in the nucleus accumbens. Nicotine (0.4 mg/kg s.c.) significantly inc reased extracellular concentrations of dopamine and of dihydroxyphenyl acetic acid (DOPAC) by 75-80% in nucleus accumbens of rats. Isoarecolo ne (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 extracell ular levels of 5-hydroxy indole acetic acid. Both nicotine and isoarec olone induced head-bobbing behaviour. Pretreatment with ketanserin red uced nicotine-induced head-bobbing suggesting a serotonergic mechanism . In conclusion, the absence of locomotor activation after administrat ion of isoarecolone may be related to its failure to activate the meso limbic dopamine system.