Periods of cocaine abstinence are associated with a high risk of relapse, often triggered by exposure to drug-associated cues. Previous research has implicated L-type calcium channels (LTCCs) in drug-seeking behaviors, yet their role in cue-induced relapse, particularly in females, remains underexplored. This study investigated the effects of LTCC inhibition on cue-induced cocaine-seeking behavior during abstinence in female Sprague-Dawley rats. Following a 10-day cocaine self-administration and a 14-day forced abstinence period, the rats were tested for cue-induced cocaine-seeking after receiving systemic administration of isradipine, a non-selective LTCC inhibitor (0.0 mg/kg, 0.1 mg/kg, 0.4 mg/kg, or 1.2 mg/kg, i.p.). Isradipine significantly reduced cue-induced cocaine-seeking in a dose-dependent manner without affecting cocaine-taking or natural reward-taking or seeking behaviors. Notably, these findings in females were comparable to our prior results observed in males, demonstrating that LTCC inhibition selectively attenuates the impact of cocaine-associated cues across sexes. These results highlight the translational potential of LTCCs as a therapeutic agent to reduce relapse risk in cocaine-dependent individuals. This study underscores the importance of considering sex-specific mechanisms in addiction treatment and calls for further research into LTCCs as a target for relapse prevention.
