Selegiline ameliorate depression-like behaviors in rodents

Study Author(s):

Toshico Ishikawa, Motoki Okano, Akiko Minami, Yuka Tsukamoto, Kazue TaKahata, Shizuco Miraoca

Journal Name:

Elsevier B.V., Behavioural Brain Research 359;353-361

Publication Date:

21th October 2018

PMID:

01664328

Selegiline, an irreversible inhibitor of monoamine oxidase (MAO)-type B, is widely prescribed for Parkinson's disease and, at higher doses, for major and atypical depression, whereby is not selectively inhibitory to both MAO-A and MAO-B activities. MAO inhibitors have been considered to function as antidepressants through MAO-A inhibition.

We have previously reported that selegiline exerts antidepressant-like effects in the mouse forced swim test (FST) via dopamine receptor D1 activation. We also tested another propargylamine MAO-B inhibitor, rasagiline. Triple subcutaneous injections (at 24, 5 and 1 hour prior to behavioural testing) with selegiline (10 mg/kg) injection, but not rasagiline (1, 3 or 10 mg/kg/injection), reduced the immobility time in the mouse FST and rat tail suspension test.

In the hippocampus and prefrontal cortex of mice, subjected to the FST, selegiline and rasagiline completely inhibited MAO-B activities. However, selegiline suppresed MAO-A activities and monoamine turnover rates at a lesser degree than rasagiline at the same doses, indicating that the antidepressant-like effects of selegiline are independent of MAO-A inhibition.

Moreover, selegiline and not rasagiline, increased the hippocampal dopamine content. Results suggest that the antidepressant-like effects of selegiline are attributable to enhancement of dopamine transmission and prevention of the impairment of the synaptic plasticity in the hippocampus.