Antidepressant-like effects of selegiline in the forced swim test

Although selegiline, a monoamine oxidase (MAO)-B inhibitor, is reported to exert antidepressant effects in depressant patients, evidence in rodents for effects of selegiline is quite limited. The purpose of the present study was to assess effects of selegiline in the forced swim test (FST) and on locomotor activity, and to investigate whether MAO inhibition or stimulation of receptors contributes to antidepressant-like effects of selegiline. Drugs were subcutaneously administrated. The single administration of reference drug nortriptyline at 5 mg/kg reduced locomotor activity without effects in FST and brain MAO activities. But nortriptyline repeatedly given 24, 5 and 1 h before behavioral tests significantly decreased an immobility time in FST without effects in motor activities, and showed weak brain MAO-B inhibition. Single and following repeated (24, 5 and 1 h before behavioral tests) administrations of selegiline at 10 mg/kg significantly decreased the immobility time in FST, with little motor stimulant effect. In contrast, (+)-methamphetamine caused a marked decrease in immobility time and an increase in locomotor activity. Selegiline at 1 and 3 mg/kg, which failed to decrease immobility time, markedly inhibited brain total-MAO and MAO-B activities. A dopamine D1 receptor antagonist SCH 23390 completely blocked antidepressant-like effects of selegiline, but not dopamine D2, serotonergic or noradrenergic receptor antagonists. These results suggest that selegiline exerts the antidepressant-like effects by prolonging escape-directed behavior rather than by a motor stimulant effect and D1 receptor activation contributes to its effect. (c) 2005 Elsevier B.V. and ECNP. All rights reserved.