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

The effect of acute or chronic treatment with the antidepressant clomiprami ne (CIM) on basal and N-methyl-D-aspartate (NMDA) evoked release of dopamin e (DA) in rat raphe has been studied using microdialysis. Acute injection o f CIM (10 or 20 mg/kg) caused a decrease in raphe DA release, as did infusi on of NMDA (25-100 mu M) into this region. When NMDA infusion was preceded by a single acute injection of CIM no differences between NMDA and NMDA plu s CIM treated groups was observed. Chronic (15 day) treatment with CIM caus ed a dose-dependent increase in basal extracelluar DA. In addition the effe ct of infusing NMDA into the raphe on DA release was markedly reduced or ab olished. This suggests that adaptive changes occur in NMDA receptor functio n during treatment with CIM. (C) 1999 Elsevier Science B.V. All rights rese rved.