Effect of antidepressant drugs on dopamine D-1 and D-2 receptor expressionand dopamine release in the nucleus accumbens of the rat

This study examined the effect of repeated treatment with the antidepressan t drugs, fluoxetine, desipramine and tranylcypromine, on dopamine receptor expression (mRNA and binding site density) in subregions of the nucleus acc umbens and striatum of the rat. The effect of these treatments on extracell ular levels of dopamine in the nucleus accumbens was also measured. Experim ents using in situ hybridisation showed that the antidepressants caused a r egion-specific increase in D-2 mRNA, this effect being most prominent in th e nucleus accumbens shell. In contrast, none of the treatments increased D- 1 mRNA in any of the regions examined. Measurement of D-2-like binding by r eceptor autoradiography, using the ligand [H-3]YM-09151-2, revealed that bo th fluoxetine and desipramine increased D-2-like binding in the nucleus acc umbens shell; fluoxetine had a similar effect in the nucleus accumbens core . Tranylcypromine, however, had no effect on D-2-like binding in the nucleu s accumbens but decreased binding in the striatum. In microdialysis experim ents, our data showed that levels of extracellular dopamine in the nucleus accumbens were not altered in rats treated with either fluoxetine or desipr amine, but increased by tranylcypromine. From our findings, we propose that the antidepressant drugs tested enhance dopamine function in the nucleus a ccumbens through either increased expression of post-synaptic D2 receptors (fluoxetine and desipramine) or increased dopamine release (tranylcypromine ).