Abstract
Upon reviewing the literature on L-DOPA in the treatment of depression, it was found that conflicting findings were reported on its usefulness as an antidepressant. We decided to investigate its potential usefulness as an antidepressant in an animal test model. In this test, a potential antidepressant should potentiate the behavioral and cardiovascular effects of yohimbine, a naturally occurring indole alkaloid, in conscious dogs. We have further investigated the interactions of L-DOPA with antagonists and drugs that potentiate its effects. Mongrel dogs were prepared aseptically by placing an indwelling cannula in the femoral artery for recording arterial pressure. Experiments were started one week post-operatively. Each dog was its own control. The effects of L-DOPA (30 mg/kg) and yohimbine (0.5 mg/kg) were recorded individually and in combination. L-DOPA produced sedative effects, whereas yohimbine produced stimulatory effects. L-DOPA failed to potentiate yohimbine effects; in fact it partially inhibited yohimbine. Ro 4-4602 (50 mg/kg), a decarboxylase inhibitor markedly inhibited the effects of L-DOPA. It was concluded that this dose of Ro 4-4602, probably also inhibited central decarboxylase. Haloperidol (0.1–0.2 mg/kg), a dopamine antagonist, completely prevented the behavioral and cardiovascular effects of L-DOPA. Following imipramine (1.5 mg/kg) pretreatment, L-DOPA failed to produce any behavioral effects. However, imipramine, when administered 10–15 min after L-DOPA, markedly increased behavioral effects but reduced the cardiovascular and emetic effects. The results of the present study are consistent with our review of the literature, finding L-DOPA not to be an antidepressant in man, but inducing, rather, motor mobilization.
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This work was supported by USPHS Grant MH-12383
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Sanghvi, I., Urquiaga, X. & Gershon, S. Exploration of the anti-depressant potential of L-DOPA. Psychopharmacologia 20, 118–127 (1971). https://doi.org/10.1007/BF00404366
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DOI: https://doi.org/10.1007/BF00404366