Involvement of dopamine receptors in the antidepressant-like effect of melatonin in the tail suspension test

Melatonin was previously shown to produce an antidepressant-like effect in the tail suspension test. In this work the mechanisms underlying its antidepressant-like effect were further studied by investigating the involvement of the dopaminergic system in its antidepressant-like effect in the tail suspension test. The effect of melatonin (1 mg/kg, i.p.) was prevented by the pretreatment of mice with haloperidol (0.2 mg/kg, i. p., a nonselective dopaminergic receptor antagonist), SCH23390 (0.05 mg/kg, s.c., a selective dopamine D1 receptor antagonist), and sulpiride (50 mg/kg, i.p., a selective dopamine D2 receptor antagonist). The i.p. administration of melatonin (0.01 mg/kg) or fluoxetine (1 mg/kg, a serotonin reuptake inhibitor) in combination with SFK38393 (0.1 mg/kg, s.c., a dopamine D1 receptor agonist) reduced the immobility time in the tail suspension test as compared with either drug alone. Moreover, the pretreatment with melatonin (0.01 mg/kg, i.p.) produced a synergistic effect with apomorphine (0.5 mu g/kg, i.p., a dopamine D2 receptor agonist), but the pretreatment with fluoxetine (1 mg/kg, i.p.) was ineffective to potentiate the effect of apomorphine. Dopamine receptor antagonists or agonists alone or in combination with melatonin did not affect locomotor activity. These results indicate that the antidepressant-like effect of melatonin in the tail suspension test is likely mediated by an interaction with the dopaminergic system, through an activation of dopamine D1 and D2 receptors. Our data confirm the previous notion on the role exerted by melatonin in depression, suggesting that it might be further investigated as an alternative for the management of depression associated with anhedonia. (C) 2010 Elsevier B.V. All rights reserved.