Molecular and circuit mechanisms regulating cocaine memory
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Cellular and Molecular Life Sciences
REVIEW
Molecular and circuit mechanisms regulating cocaine memory Brooke N. Bender1,2 · Mary M. Torregrossa1,2 Received: 17 September 2019 / Revised: 4 February 2020 / Accepted: 2 March 2020 © Springer Nature Switzerland AG 2020
Abstract Risk of relapse is a major challenge in the treatment of substance use disorders. Several types of learning and memory mechanisms are involved in substance use and have implications for relapse. Associative memories form between the effects of drugs and the surrounding environmental stimuli, and exposure to these stimuli during abstinence causes stress and triggers drug craving, which can lead to relapse. Understanding the neural underpinnings of how these associations are formed and maintained will inform future advances in treatment practices. A large body of research has expanded our knowledge of how associative memories are acquired and consolidated, how they are updated through reactivation and reconsolidation, and how competing extinction memories are formed. This review will focus on the vast literature examining the mechanisms of cocaine Pavlovian associative memories with an emphasis on the molecular memory mechanisms and circuits involved in the consolidation, reconsolidation, and extinction of these memories. Additional research elucidating the specific signaling pathways, mechanisms of synaptic plasticity, and epigenetic regulation of gene expression in the circuits involved in associative learning will reveal more distinctions between consolidation, reconsolidation, and extinction learning that can be applied to the treatment of substance use disorders. Keywords Learning · Addiction · Consolidation · Reconsolidation · Extinction
Introduction Memories related to obtaining positive outcomes promote continued reward-seeking behavior that is important for survival. Unfortunately, when the outcome is a drug of abuse, these memories can become abnormally strong and maladaptive, thus promoting drug use over other behaviors. Even during abstinence, exposure to environmental cues associated with drug use can trigger memories that elicit craving, cause physiological stress, and initiate drug-seeking behaviors that lead to relapse [1–4]. Uncovering the mechanisms underlying the formation and retrieval of these drug memories may reveal ways to improve treatment and prevent relapse [5]. Much of the research focused on understanding the neural underpinnings of drug-associated memories has focused on memories formed during exposure to cocaine * Mary M. Torregrossa [email protected] 1
Department of Psychiatry, University of Pittsburgh, 450 Technology Drive, Pittsburgh, PA 15219, USA
Center for Neuroscience, University of Pittsburgh, 4200 Fifth Ave, Pittsburgh, PA 15213, USA
2
as the drug of abuse [6]. Cocaine use disorder remains a prominent burden on society, and cocaine use continues to increase [7]. Furthermore, there has been an increase in overdose deaths involving concomitant cocaine and heroin use [7]. Finally, identifi
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