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Review
. 2025 Aug:175:106217.
doi: 10.1016/j.neubiorev.2025.106217. Epub 2025 May 21.

Mechanistic and translational insights from preclinical cocaine choice procedures on the economic substitutability of cocaine and nondrug reinforcers

Madison M Marcus  1 , Matthew L Banks  2
Affiliations
Review

Mechanistic and translational insights from preclinical cocaine choice procedures on the economic substitutability of cocaine and nondrug reinforcers

Madison M Marcus et al. Neurosci Biobehav Rev. 2025 Aug.

Abstract

Substance use disorders are increasingly being conceptualized as behavioral misallocation disorders; however, the neurobiological determinants of this behavioral misallocation are poorly understood. Cocaine use disorder (CUD) develops as a result of behavior being disproportionally directed towards the procurement and use of cocaine at the expense of behaviors maintained by more adaptive, nondrug reinforcers (i.e., job, family). Preclinical cocaine-vs-nondrug reinforcer choice procedures are uniquely positioned to 1) elucidate the biological mechanisms of drug and nondrug reinforcement and 2) inform the development of effective pharmacological and behavioral CUD therapies. Accordingly, this review addresses the existing preclinical literature regarding the economic substitutability and mesolimbic dopaminergic mechanisms underlying cocaine self-administration in the context of three different concurrently available nondrug reinforcers: food, social interaction, and electric foot shock (a negative reinforcer). The manuscript focuses on how the existing cocaine-vs-nondrug reinforcer choice literature guides future research directions to facilitate advances in understanding of CUD from both a neuroscience and translational research perspective.

Keywords: Behavioral economics; Cocaine; Dopamine; Drug choice; Negative reinforcement; Social interaction; Substance use disorder.

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