Abstract
This study describes the effects of melatonin on cocaine-induced anxiety-like behavior and nucleus accumbens (NAc) cAMP levels in rats. Animals drinking a solution of melatonin (200 ng/ml) at night, either during repeated cocaine administration (15 mg/kg i.p., twice a day for 9 days) or during its withdrawal, showed less anxiety-like behavior in a defensive withdrawal paradigm 48 h after the last injection of cocaine. Melatonin did not alter behavior in control rats treated with saline. Animals exposed for 1 week to unrestricted free-choice oral melatonin self-administration (200 ng/ml) did not show preference for the drinking solution containing melatonin. Pretreatment with melatonin (200 ng/kg i.p. or 200 ng/ml orally) significantly attenuated the augmentation of cAMP levels in NAc following acute cocaine administration (15 mg/kg i.p.). Taken together, these results suggest that a low-dose night-time melatonin treatment results in anxiolytic-like effects in rats withdrawn from repeated cocaine administration, can antagonize cocaine-induced activation of NAc cAMP levels and has low dependence liability.
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