Effect of antidepressant drugs on dopamine D1 and D2 receptor expression and dopamine release in the nucleus accumbens of the rat

Abstract

This study examined the effect of repeated treatment with the antidepressant drugs, fluoxetine, desipramine and tranylcypromine, on dopamine receptor expression (mRNA and binding site density) in sub-regions of the nucleus accumbens and striatum of the rat. The effect of these treatments on extracellular levels of dopamine in the nucleus accumbens was also measured. Experiments using in situ hybridisation showed that the antidepressants caused a region-specific increase in D₂ mRNA, this effect being most prominent in the nucleus accumbens shell. In contrast, none of the treatments increased D₁ mRNA in any of the regions examined. Measurement of D₂-like binding by receptor autoradiography, using the ligand [³H]YM-09151-2, revealed that both fluoxetine and desipramine increased D₂-like binding in the nucleus accumbens shell; fluoxetine had a similar effect in the nucleus accumbens core. Tranylcypromine, however, had no effect on D₂-like binding in the nucleus accumbens but decreased binding in the striatum. In microdialysis experiments, our data showed that levels of extracellular dopamine in the nucleus accumbens were not altered in rats treated with either fluoxetine or desipramine, but increased by tranylcypromine. From our findings, we propose that the antidepressant drugs tested enhance dopamine function in the nucleus accumbens through either increased expression of postsynaptic D₂ receptors (fluoxetine and desipramine) or increased dopamine release (tranylcypromine).