Chronic but not acute clomipramine alters the effect of NMDA receptor regulation of dopamine release in rat frontal cortex

The effect of acute or chronic treatment with the antidepressant clomiprami ne (CIM) on N-methyl-D-aspartate (NMDA) evoked release of dopamine (DA) in the frontal cortex of the rat has been studied using microdialysis. Acute i njection of CIM (10 or 20 mg/kg) caused a decrease in dialysate DA in the f rontal cortex. Infusion of 25-100 mu M NMDA into the frontal cortex decreas ed DA release in this region. When NMDA infusion was preceded by a single i njection of CIM no marked differences between NMDA and NMDA + CIM treated g roups were observed. Chronic (15 day) treatment with CIM (10 or 20 mg/kg) c aused a dose-dependent increase in basal extracellular DA. In these animals , however, the effects of infusion of NMDA on DA release in the cortex were greatly attenuated or abolished. This suggests that adaptive changes occur in NMDA receptor function during treatment with an antidepressant. The pos sible significance of this in the aetiology and treatment of depression is discussed. (C) 1999 Elsevier Science Ireland Ltd. Ail rights reserved.