L-type calcium channel blockade attenuates the anxiogenic-like and pro-depressive-like effects of cocaine abstinence in female and male rats.

Cocaine abstinence and withdrawal are linked to relapse, heightened anxiety, and depressive-like symptoms. While L-type calcium channels (LTCCs) have been associated with cocaine use disorders in humans and drug-seeking behavior in rodent models, their role in mood-related symptoms during cocaine abstinence remains unclear. This study examined whether blocking LTCCs with isradipine could alter anxiety and depressive symptoms induced by cocaine abstinence. Male and female Sprague-Dawley rats self-administered cocaine or saline, followed by 14 days of abstinence without access to cocaine or saline. They were then assessed for anhedonia, anxiety, and depressive-like behaviors using the sucrose preference test (SPT), elevated plus maze (EPM), and forced swim test (FST). Cocaine-abstinent rats showed increased anxiogenic and pro-depressive responses in the EPM and FST, compared to saline-abstinent rats. However, cocaine abstinent rats showed no changes in the SPT. Systemic administration of isradipine (0.4 mg/kg or 1.2 mg/kg, I.P.), reversed the anxiogenic-like behaviors in female cocaine-abstinent rats, whereas only the higher dose of isradipine (1.2 mg/kg, i.p.) was effective in male cocaine-abstinent rats. In the FST, the lower dose (0.4 mg/kg, i.p.) of isradipine reversed the increased immobility time observed in control cocaine-abstinent female and male rats, with no effect of isradipine on its own in saline-abstinent rats. In contrast the 1.2 mg/kg, i.p. decreased immobility time in both cocaine and saline abstinent female and male rat. In summary, isradipine reversed anxiety and depressive effects associated with cocaine abstinence in a dose- and sex-dependent manner.