Interactions between imidazoline binding sites and dopamine levels in the rat nucleus accumbens

Imidazoline binding sites are present in the striatal complex and in the ex tended amygdala and have been implicated in mood disorders. In this report we analysed the influence of these sites on the functional activity of the mesolimbic dopaminergic transmission, one of the major brain systems involv ed in the regulation of motivation and reward. We studied the effects of tw o imidazoline ligands, S23229 and S23230 (respectively S(+) and R(-) enanti omers of the S22687 or (5-[2-methyl phenoxy methyl] 1,3-oxazolin-2-yl) amin e), on extracellular dopamine in the nucleus accumbens using microdialysis in freely moving rats. We compared these imidazoline ligands to cocaine, a dopamine uptake blocker known to increase extracellular dopamine concentrat ions. S23229 dose-dependently increased extracellular dopamine and locomoto r activity. S23230 dose-dependently increased extracellular dopamine and pr oduced a near-significant dose-effect on locomotor activity. S23229 had a s tronger efficacy than S23230 and increased dopamine levels in the nucleus a ccumbens at an extent similar to the one of cocaine. These results suggest that central imidazoline binding sites could contribute to the functional r egulation of the mesolimbic dopaminergic system.