Chronic clomipramine administration reverses NMDA-evoked decreases in dopamine release in the raphe nuclei.

The effect of acute or chronic treatment with the antidepressant clomipramine (CIM) on basal and N-methyl-d-aspartate (NMDA) evoked release of dopamine (DA) in rat raphe has been studied using microdialysis. Acute injection of CIM (10 or 20 mg/kg) caused a decrease in raphe DA release, as did infusion of NMDA (25-100 microM) into this region. When NMDA infusion was preceded by a single acute injection of CIM no differences between NMDA and NMDA plus CIM treated groups was observed. Chronic (15 day) treatment with CIM caused a dose-dependent increase in basal extracellular DA. In addition the effect of infusing NMDA into the raphe on DA release was markedly reduced or abolished. This suggests that adaptive changes occur in NMDA receptor function during treatment with CIM.