This study examined whether blocking L-type calcium channels (LTCCs) could reduce anxiety-like behaviors caused by cocaine withdrawal in rats. The researchers aimed to determine if isradipine, an LTCC blocker, could alleviate mood-related symptoms during cocaine abstinence in both female and male rats.

Cocaine withdrawal often leads to anxiety-like and depression-related symptoms, which can trigger relapse. Understanding how to mitigate these symptoms is crucial for developing effective treatments. This research is significant as it explores a potential therapeutic use for isradipine, a drug already approved for treating high blood pressure, in addressing mood disorders associated with cocaine abstinence. These findings could inform future treatments for cocaine use disorder and related mood disorders.

The researchers used adult Sprague-Dawley rats, training them to self-administer cocaine or saline for 10 days. Following a 14-day abstinence period, the rats underwent behavioral tests, including the sucrose preference test (SPT), elevated plus maze (EPM), and forced swim test (FST). Isradipine was administered at varying doses to evaluate its effects on anxiety and depression-like behaviors during abstinence.

Cocaine-abstinent rats displayed increased anxiety-like behavior, spending less time in the open arms of the EPM, and showed greater immobility in the FST, indicating depressive-like symptoms. Isradipine effectively reduced these symptoms in a dose-dependent manner. In female rats, both low and high doses of isradipine reduced anxiety-like behaviors, while in males, only the high dose was effective. Isradipine also decreased immobility time in both cocaine and saline-abstinent rats, though the low dose was only effective in cocaine-abstinent rats.

These results suggest that isradipine could be a promising treatment for mood disorders during cocaine withdrawal. The study highlights sex differences in response to isradipine, suggesting that female and male patients might require different dosing strategies. This research supports further exploration of LTCC blockers as potential therapies for mood symptoms in cocaine use disorder.

The authors recommend further studies to explore the mechanisms by which isradipine affects mood-related behaviors during cocaine abstinence. Future research should also investigate the role of sex hormones, such as estrogen, in modulating LTCC activity and the effectiveness of isradipine in treating mood disorders associated with cocaine use.

Cocaine-trained female rats showed a significant lever effect (F(1, 110) = 555.3, p < 0.05) and lever x day interaction (F(9, 110) = 17.99, p < 0.05). Male rats also showed a significant lever effect (F(1, 110) = 605.3, p < 0.05) and lever x day interaction (F(9, 110) = 20.08, p < 0.05). In the EPM, cocaine abstinent rats spent less time in open arms (F(1, 104) = 12.74, p < 0.05). In the FST, a significant isradipine effect was found on immobility time (F(2, 94) = 32.12, p < 0.05) and sex effect (F(1, 94) = 4.430, p < 0.05).

This research was funded by the National Institute of Drug Abuse (awards R01 DA050454 and R01 DA053261). The research also received support from the State of Connecticut, Department of Mental Health and Addiction Services. This publication does not express the views of the Department of Mental Health and Addiction Services or the State of Connecticut, nor the National Institutes of Health.