Selective inhibition of MAO-A, not MAO-B, results in antidepressant-like effects on DRL 72-s behavior.
The effects of monoamine oxidase inhibitors (MAOIs) that selectively inhibit the MAO-A or MAO-B forms of MAO were studied in rats performing under a differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule of reinforcement. Clorgyline and CGP11'305A, irreversible and reversible MAO-A inhibitors, respectively, increased the reinforcement rate, decreased the response rate, and enhanced temporal discrimination. The irreversible MAO-B inhibitor (-)-deprenyl did not produce similar effects. Pargyline did not increase the reinforcement rate at low doses that selectively inhibit MAO-B, but did increase the reinforcement rate at doses that inhibit MAO-A by more than 90%. The present results are in accord with clinical data demonstrating that MAO-A inhibitors are effective therapeutic agents in treating depression while MAO-B inhibitors are of questionable antidepressant efficacy. The present findings provide further evidence that the DRL 72-s schedule may be useful both as a screen for identifying new antidepressants and for investigating the neurochemical effects of antidepressant drugs that are responsible for their therapeutic effects.
Marek
G J
GJ
Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60637.
Seiden
L S
LS
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003010:Clorgyline / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010293:Pargyline / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012055:Reinforcement Schedule; D012642:Selegiline / Q000494:pharmacology
D000928:Antidepressive Agents; D008996:Monoamine Oxidase Inhibitors; D010880:Piperidines; D012642:Selegiline; C038213:brofaromine; D010293:Pargyline; D003010:Clorgyline