Agomelatine decreased cocaine-induced locomotor activity in rats; a dose-time response study

Agomelatine (Valdoxa) is a melatonin-like antidepressant that has been shown to decrease cocaine-induced locomotor activity and dopamine release when administered at 10 mg/kg for 10 days. While major depressive disorder is typically treated with an initial dose of 25 mg/day, titrated to 50 mg/day, such dosing is unlikely for cocaine use disorder (CUD). This is due to the long-term nature of CUD treatment, the hepatotoxicity associated with high and prolonged agomelatine doses, and the increased risk of liver disease in CUD patients.

Given these considerations, this study aimed to determine an effective agomelatine dosing schedule for CUD by evaluating various doses (5, 10, or 40 mg/kg) and administration durations (0, 10, or 30 days) in a locomotor sensitization model.

The study's results showed that: agomelatine doses of 10 mg/kg or higher significantly decreased long-term cocaine-induced locomotor activity during the expression phase. This effect was observed regardless of whether agomelatine was administered on the first day (day 0) or after 10 or 30 days of cocaine withdrawal. Specifically, 10 mg/kg of agomelatine given for 10 days during cocaine withdrawal attenuated long-term locomotor activity induced by various cocaine doses (5, 10, or 20 mg/kg) during the expression phase. Additionally, a 30 mg/kg dose of agomelatine administered for 10 days decreased locomotor activity induced by binge-pattern cocaine administration.

Collectively, these findings suggest that a dosage of 10 mg/kg of agomelatine administered for 10 consecutive days effectively attenuates the long-term behavioral effects of cocaine.