Abstract
The majority of individuals with cocaine use disorder engage in polysubstance use. Alcohol is commonly used together with cocaine. Cocaine and alcohol produce distinct and sometimes opposing effects on the glutamate neurotransmitter system in the nucleus accumbens. Nucleus accumbens glutamate has been demonstrated to play a significant role in relapse to cocaine and alcohol seeking. Here we review the literature on the known effects of cocaine and alcohol monosubstance and polysubstance use on nucleus accumbens glutamate. While relapse to both cocaine and alcohol seeking are accompanied by the release of glutamate in the NA core, relapse to cocaine-seeking in a cocaine+alcohol polysubstance model is not. Furthermore, while the beta-lactam ceftriaxone is effective at attenuating the reinstatement of cocaine and alcohol seeking in monosubstance models, it is not in a cocaine+alcohol polysubstance model, likely because a different neurocircuitry of relapse has been engaged by polysubstance use. Taken together, the literature reviewed here finds that cocaine+alcohol polysubstance use produces distinct neuroadapations in the nucleus accumbens core. These findings have relevance for the development of pharmacotherapeutics to reduce the risk of relapse to cocaine seeking.
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Knackstedt, L. (2022). Linking Polysubstance Use, Glutamate, and the Nucleus Accumbens. In: Patel, V.B., Preedy, V.R. (eds) Handbook of Substance Misuse and Addictions. Springer, Cham. https://doi.org/10.1007/978-3-030-92392-1_153
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