Inhibition of MAO-A fails to alter cocaine-induced increases in extracellular dopamine and norepinephrine in rat nucleus accumbens

Monoamine oxidase (MAO) inhibitors are being investigated as possible medic ations for cocaine dependence, but there: are potential problems with this approach. In the present study, we tested the hypothesis that inhibition of catecholamine metabolism with the MAO-A inhibitor, clorgyline, might enhan ce cocaine-induced increases in extracellular dopamine and norepinephrine i n rat nucleus accumbens. Male rats were pretreated with clorgyline (1 mg/kg , s.c.) or its saline vehicle (1 ml/kg, s.c.), and microdialysis probes wer e inserted into previously implanted guide cannulae. After overnight perfus ion of the probes in situ, rats received an acute challenge injection of ei ther cocaine (1 mg/kg, i.v.) or its saline vehicle (1 ml/kg, i.v.). Clorgyl ine pretreatment alone caused significant elevations in basal levels of dia lysate norepinephrine but not dopamine. Cocaine administration elicited sig nificant increases in extracellular dopamine and norepinephrine in all grou ps of rats, and this effect was not altered by clorgyline pretreatment. The 1 mg/kg dose of clorgyline decreased dopamine metabolites in postmortem br ain tissue by more than 80%. Our data are consistent with clinical studies that demonstrate pretreatment with the MAO-B selective inhibitor, selegelin e, fails to alter cocaine-induced subjective effects in human drug users. M oreover, these findings suggest that adverse consequences related to altere d catecholamine transmission would not occur if patients taking phenelzine, a non-selective MAO inhibitor, relapsed and used cocaine. (C) 2001 Elsevie r Science B.V. All rights reserved.