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Aerobic exercise attenuates reinstatement of cocaine-seeking behavior and associated neuroadaptations in the prefrontal cortex.

ABSTRACT: Exercise has recently been suggested as an attractive alternative to pharmacotherapy for treating drug addiction. The goal of this study was to determine, using an animal model, whether aerobic exercise may block reinstatement of cocaine-seeking and its underlying neurobiology (i.e., neuronal signaling in the prefrontal cortex).Following acquisition and 10 days of 24-hour access to cocaine (1.5 mg/kg/infusion) or saline under a discrete trial procedure (four infusions/hr), rats began a 14-day abstinence period. During this period, rats were either given access to a running-wheel for 2-hours each day or placed in similar boxes with the wheel locked. Cocaine-seeking was assessed following the 14th day of abstinence using a within-session extinction/cue-induced reinstatement procedure. Neuronal activity was assessed by examining phosphorylated levels of extracellular signal-regulated kinase (pERK) using Western blot analysis.Wheel running reduced cocaine-seeking during both extinction and reinstatement. Cocaine-seeking was positively associated with pERK levels in the prefrontal cortex. Although pERK levels were not different among saline controls, in the cocaine group, pERK levels were significantly decreased by exercise.Aerobic exercise may reduce relapse vulnerability by preventing the increase in cocaine-seeking and associated neuroadaptations in the prefrontal cortex that develop over an abstinence period.

SUBMITTER: Lynch WJ

PROVIDER: S-EPMC2949528 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

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Aerobic exercise attenuates reinstatement of cocaine-seeking behavior and associated neuroadaptations in the prefrontal cortex.

Lynch Wendy J WJ Piehl Kristen B KB Acosta Glen G Peterson Alexis B AB Hemby Scott E SE

Biological psychiatry 20100808 8

<h4>Background</h4>Exercise has recently been suggested as an attractive alternative to pharmacotherapy for treating drug addiction. The goal of this study was to determine, using an animal model, whether aerobic exercise may block reinstatement of cocaine-seeking and its underlying neurobiology (i.e., neuronal signaling in the prefrontal cortex).<h4>Methods</h4>Following acquisition and 10 days of 24-hour access to cocaine (1.5 mg/kg/infusion) or saline under a discrete trial procedure (four in ...[more]

PMID: 20692647

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Project description:IntroductionWomen have a shorter course from initial cocaine use to meeting the criteria for cocaine use disorder as compared to men. Preclinical findings similarly indicate that females develop key features of an addiction-like phenotype faster than males, including an enhanced motivation for cocaine and compulsive use, indicating that this phenomenon is biologically based. The goals of this study were to determine whether cocaine-craving, another key feature of addiction, also develops sooner during withdrawal in females than males and to determine whether there are sex differences in the molecular mechanisms associated with its development focusing on markers known to mediate cocaine-craving in males (i.e., dorsomedial prefrontal cortex, dmPFC, expression of brain-derived neurotrophic factor exon-IV, Bdnf-IV, and NMDA receptor subunits, Grin2a, Grin2b, and Grin1).MethodsCocaine-craving was assessed following extended-access cocaine self-administration and 2, 7, or 14 days of withdrawal using an extinction/cue-induced reinstatement procedure. Tissue was obtained from the dmPFC immediately after reinstatement testing and gene expression changes were analyzed using real-time qPCR.ResultsIn males, cocaine-craving (total extinction and cue-induced reinstatement responding) progressively increased from early to later withdrawal time-points whereas in females, cocaine-craving was already elevated during early withdrawal (after 2 days) and did not further increase at later withdrawal time-points. Levels of cocaine-craving, however, were similar between the sexes. Gene expression changes differed markedly between the sexes such that males showed the expected relapse- and withdrawal-associated changes in Bdnf-IV, Grin2a, Grin2b, and Grin1 expression, but females only showed a modest increase Grin1 expression at the intermediate withdrawal timepoint.DiscussionThese findings indicate that cocaine-craving is similarly expressed in males and females although the time-course for its incubation appears to be accelerated in females; the molecular mechanisms also likely differ in females versus males.

Dataset Information

Aerobic exercise attenuates reinstatement of cocaine-seeking behavior and associated neuroadaptations in the prefrontal cortex.

Publications

Aerobic exercise attenuates reinstatement of cocaine-seeking behavior and associated neuroadaptations in the prefrontal cortex.

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