Dopamine is involved in the antidepressant-like effect of allopregnanolone in the forced swimming test in female rats

Evidence from both animal and human studies suggests a role for dopamine in the therapeutic effect of antidepressant drugs. Consistently, dopamine receptor antagonists antagonize the effect of antidepressant drugs in different experimental models of depression. Neurosteroids, and in particular allopregnanolone, seem to be involved both in the pathophysiology of depression and in the mechanism of action of antidepressant drugs, and their role seems to be particularly important in the understanding of mood disturbances related to the different phases of the reproductive life in women. The aim of this study was to investigate the possible role of dopamine on the antidepressant-like effect of allopregnanolone in a model of depression. Thus, we examined (i) the behaviour of female Sprague-Dawley rats in the forced swimming test during estrus and diestrus and their response to allopregnanolone treatment (0.5, 1 and 2 mg/kg), and (ii) the effect of the dopamine D1-like and D2-like receptor antagonists SCH 23390 (0.01 and 0.025 mg/kg) and raclopride (0.05 and 0.2 mg/kg) on the antidepressant-like effect of allopregnanolone (2 mg/kg) in the same experimental model. We failed to observe differences in depressive-like behaviour between estrous phases, and allopregnanolone administration in both estrus and diestrus resulted in an antidepressant-like effect consisting in an increase of swimming behaviour. The allopregnanolone effect was unaffected by a dose of the dopamine D1-like receptor antagonist SCH 23390 displaying a marked inhibitory effect on basal activity, while it was turned into a potentiation of the depressive-like behaviour of the forced swimming condition by treatment with the higher dose of raclopride. The present results indicate an involvement of dopamine transmission in the allopregnanolone antidepressant-like effect in the forced swimming model of depression, and suggest that this effect depends mainly on stimulation of dopamine D2-like receptors. Behavioural Pharmacology 21:21-28 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.