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 clomipramine (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 injection of CIM (10 or 20 mg/kg) caused a decrease in dialysate DA in the frontal cortex. Infusion of 25-100 microM NMDA into the frontal cortex decreased DA release in this region. When NMDA infusion was preceded by a single injection of CIM no marked differences between NMDA and NMDA + CIM treated groups were observed. Chronic (15 day) treatment with CIM (10 or 20 mg/kg) caused 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 possible significance of this in the aetiology and treatment of depression is discussed.
Pallotta
M
M
Istituti Di Farmacologia i Tossicologia, Facolta Di Medicina E Chirugia, Universita Degli Studi Di Napoli, Frederico II, Italy.
Segieth
J
J
Whitton
P S
PS
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D002997:Clomipramine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D007263:Infusions, Parenteral; D007274:Injections, Intraperitoneal; D008297:Male; D017551:Microdialysis; D016202:N-Methylaspartate / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D000928:Antidepressive Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D002997:Clomipramine; D004298:Dopamine