Effects of escitalopram and imipramine on cocaine reinforcement and drug-seeking behaviors in a rat model of depression

Abstract

Depression and substance cocaine abuse are disorders with a high frequency of comorbidity. In the present study, we combined bilateral olfactory bulbectomy (OBX), an animal model of depression, with intravenous cocaine self-administration and extinction/reinstatement in rats to investigate the effects of two antidepressant drugs, escitalopram (ESC) and imipramine (IMI), with the goal of determining whether these drugs altered cocaine-induced reinforcement and seeking behaviors.Acute administration of IMI (2.5–30mg/kg) reduced the cocaine reinforcement in OBX and SHAM rats. Moreover, IMI effectively reduced the cocaine-seeking behavior after the drug acute or repeated administration during extinction training in OBX rats and SHAM-operated controls. By contrast, acutely administered ESC (2.5–20mg/kg) did not alter cocaine reinforcement in OBX rats or SHAM-operated controls. The lack of ESC effects was also demonstrated during reinstatement tests to study drug-seeking behavior after ESC repeated daily treatment during extinction trials. However, acute treatment with ESC dose-dependently decreased the cocaine-seeking behavior and relapse triggered by cocaine priming or drug-associated conditioned cues in both OBX and SHAM rats.These results indicate the cocaine anti-reinforcement and anti-seeking efficacy of the two antidepressant drugs studied here. However, the mechanisms for the IMI and ESC activity should be clarified in further studies.