Hypericum perforatum L. prevents the acquisition of and promotes resilience against stress-induced reinstatement of the conditioned place preference induced by cocaine

• Published in: Neuroscience letters Vol. 762; p. 136164
• Main Authors: Fugazzotto, Federica, Occhiuto, Francesco, García-Pardo, Maria P., Aguilar, Maria A.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 25-09-2021
• Subjects: Animals; Cocaine; Cocaine-Related Disorders; Conditioned place preference; Conditioning, Classical - drug effects; Extinction, Psychological - drug effects; Hypericum; Hypericum perforatum L; Male; Mice; Plant Extracts - pharmacology; Reinstatement; Social defeat; NAT; Hypericum perforatum L; CPP; Post-C; Conditioned place preference; Pre-C; Hypericum; TLC; Social defeat; SD; LC-MS; SERT; NA; DAT; Reinstatement; Cocaine; Mice; 5-HT; EMCDDA; DA; HPLC
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2021.136164

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•Hypericum perforatum L. does not induce conditioned place preference in mice.•Hypericum perforatum L. blocks the acquisition of cocaine-induced place preference.•Hypericum perforatum L. prevents stress-induced reinstatement of cocaine preference.
Cocaine use disorder is a serious problem worldwide, and there are no approved medications for its treatment. A novel approach to the treatment of drug addiction is the use of natural products, and, in this context, preclinical evidence suggests that Hypericum perforatum L. (Hypericum) is effective against alcohol and other substance use disorders. We hypothesised that Hypericum could also be useful as a treatment for cocaine use disorder, and so we set out to test its effectiveness in a mice model of cocaine addiction. In the first experiment we evaluated its effects on the acquisition of cocaine-induced conditioned place preference (CPP). Adult male mice were conditioned with cocaine (25 mg/kg), cocaine with Hypericum (75, 150 or 300 mg/kg) or the plant extract alone (300 mg/kg). In the second experiment, we tested the effects of Hypericum on stress-induced reinstatement of cocaine CPP. All the mice were conditioned with cocaine (25 mg/kg) and, after extinction of CPP, the reinstating effects of social defeat (alone or with 75, 150 or 300 mg/kg of Hypericum) were evaluated. All the doses of Hypericum prevented the acquisition of cocaine-induced CPP. Furthermore, the plant extract dose-dependently reduced the reinstating effects of social defeat. Therefore, Hypericum is effective in reducing the rewarding effects of cocaine and prevents the stress-induced reinstatement of cocaine CPP in mice. The mechanisms underlying these positive effects of Hypericum perforatum L. need to be determined by future research. Our results endorse Hypericum as a natural treatment for cocaine dependence.