Circadian-dependent effect of melatonin on dopaminergic D 2 antagonist-induced hypokinesia and agonist-induced stereotypies in rats

Abstract

Although a melatonin/dopamine relationship has been well established in nonmotor systems wherein dopamine and melatonin share an antagonist relationship, less clear is the role melatonin may play in extrapyramidal dopaminergic function. Therefore, the purpose of the present experiments was to examine the relationship between melatonin and the dopaminergic D 2 receptor system and behavior. Hypokinesia was induced in male Sprague–Dawley rats with fluphenazine (D 2 antagonist, 0.4 mg/kg ip) and stereotypies with apomorphine (D 2 agonist, 0.6 mg/kg sc) during the light (1200 h) and dark (2200 h) phases. As expected, fluphenazine induced severe hypokinesia during the light phase (482±176 s); however, unexpectedly, fluphenazine-induced hypokinesia during the dark was almost nonexistent (25±6 s). Furthermore, melatonin treatment (30 mg/kg ip) produced a strong interaction with fluphenazine in that it reduced fluphenazine-induced hypokinesia by nearly 80% in the light (112±45 s) but paradoxically increased the minimal fluphenazine-induced hypokinesia in the dark by more than 60% (70±17 s). Melatonin also reduced apomorphine-induced stereotypies by nearly 40% in the light but had no effect in the dark. Taken together, these data show (1) a strong and unexpected nocturnal effect of fluphenazine on hypokinesia and (2) provide support for an antagonistic melatonin/dopaminergic interaction in the context of motor behavior and D 2 receptor function which appears to be critically dependent on the light/dark status of the dopaminergic system.