Idazoxan preferentially increases dopamine output in the rat medial prefrontal cortex at the nerve terminal level.

The effects of the alpha2-adrenoceptor antagonist idazoxan on extracellular concentrations of dopamine in major dopaminergic terminal regions in the brain were investigated by means of microdialysis in freely moving rats. Systemic administration of idazoxan markedly increased dopamine output in the medial prefrontal cortex, whereas it failed to affect dopamine efflux in the striatum or in the nucleus accumbens. Local perfusion of idazoxan via reversed dialysis markedly enhanced dopamine efflux in cortical but not subcortical areas, in which dopamine output was but little affected. Infusion of idazoxan into the ventral tegmental area did not alter the dopamine efflux in the medial prefrontal cortex. Moreover, the increase in cortical dopamine efflux induced by systemic administration of idazoxan was unaffected by tetrodotoxin perfusion of the ventral tegmental area. These data show that the alpha2-adrenoceptor antagonist idazoxan preferentially increases basal dopamine output in the medial prefrontal cortex through a local mechanism, an effect which appears largely independent of dopaminergic neuronal activity. An enhanced output of cortical dopamine may contribute to the purported augmentation by alpha2-adrenoceptor antagonists of the therapeutic effects of both antidepressant and antipsychotic drugs.