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bioRxiv · 10.1101/2021.09.05.458975

Metformin in nucleus accumbens core reduces cue-induced cocaine seeking in male and female rats

Chan, A.·Willard, A.·Mulloy, S.·Ibrahim, N.·Sciaccotta, A.·Schonfeld, M.·Spencer, S.
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Abstract

This study investigated the potential therapeutic effects of the FDA-approved drug metformin on cue-induced reinstatement of cocaine seeking. Metformin (dimethyl-biguanide) is a first-line treatment for type II diabetes that, among other mechanisms, is involved in the activation of adenosine monophosphate activated protein kinase (AMPK). Cocaine self-administration and extinction is associated with decreased levels of phosphorylated AMPK within the nucleus accumbens core (NAcore). Previously it was shown that increasing AMPK activity in the NAcore decreased cue-induced reinstatement of cocaine seeking. Decreasing AMPK activity produced the opposite effect. The goal of the present study was to determine if metformin in the NAcore reduces cue-induced cocaine seeking in adult male and female Sprague Dawley rats. Rats were trained to self-administer cocaine followed by extinction prior to cue-induced reinstatement trials. Metformin microinjected in the NAcore attenuated cue-induced reinstatement in male and female rats. Importantly, metformins effects on cocaine seeking were not due to a general depression of spontaneous locomotor activity. In female rats, metformins effects did generalize to a reduction in cue-induced reinstatement of sucrose seeking. These data support a potential role for metformin as a pharmacotherapy for cocaine use disorder, but warrant caution given the potential for metformins effects to generalize to a natural reward in female rats.

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Chan, A., Willard, A., Mulloy, S., Ibrahim, N., Sciaccotta, A., Schonfeld, M., Spencer, S.. 2021-09-06. Metformin in nucleus accumbens core reduces cue-induced cocaine seeking in male and female rats. https://doi.org/10.1101/2021.09.05.458975

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