Selective inhibition of MAO-A, not MAO-B, results in antidepressant-like effects on DRL 72-s behavior

Abstract

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.

BIMT 17: a putative antidepressant with a fast onset of action?

“…BIMT 17 shifted the PkL toward shorter IRT durations while imipramine shifted PkL toward longer IRT durations. Previous research (Seiden et al 1985;Marek and Seiden 1988a;Richard et al 1993b) has shown that a variety of antidepressant compounds shift the peak of the IRT distribution toward longer IRT durations without decreasing PkA. This shift in the IRT distribution toward longer waiting times results in an increased reinforcement rate.…”

The effects of selected antidepressant drugs on timing behaviour in rats

“…It has been claimed that the number of reinforcements earned by rats in the DRL 72 s schedule can be increased by the administration of compounds which have antidepressant e¤ects in man (ODonnell and Seiden 1983). This claim has been supported by a number of studies which have examined a wide variety of antidepressant treatments on DRL 72 s schedule behaviour, including 5-HTP (a 5-HT precursor with antidepressant e¦cacy; Marek et al 1989a), tricyclic antidepressants (McGuire and Seiden 1980a), monoamine oxidase inhibitors (ODonnell and Seiden 1982;Marek and Seiden 1988a), 5-HT reuptake inhibitors (Marek et al 1989a), 5-HT 2 antagonists (Marek et al 1989b) and electroconvulsive shock (Seiden et al 1985). In contrast, non-antidepressant treatments are reported to decrease the reinforcement rate on the DRL 72 s schedule (ODonnell and Seiden 1983).…”

Differential modulation of efficiency in a food-rewarded "differential reinforcement of low-rate" 72-s schedule in rats by norepinephrine and serotonin reuptake inhibitors

“…Thus, monoamine oxidase inhibitors (O'Donnell and Seiden 1982;Marek and Seiden 1988a) and electroconvulsive shock (Seiden et al 1985) enhance efficiency both by an increase in reinforcement rates and a simultaneous decrease in response rates. Further, the "atypical" agents mirtazapine and mianserin, which possess 5-HT 2C and α 2 -adrenoceptor (AR) antagonist properties, similarly improve DRL 72-s performance by increasing reinforcement rates and/or decreasing response rates (O'Donnell and Seiden 1983;Marek et al 1989b;Hand et al 1991;Jackson et al 1995;Jones et al 1998).…”