Replication and extension of the subregion selectivity of glutamate-related changes within the nucleus accumbens associated with the incubation of cocaine-craving.

Autor: Webb SM; Department of Psychological and Brain Sciences, MC-9660, University of California Santa Barbara, Santa Barbara, CA 93106-9660, United States of America., Miller BW; Department of Psychological and Brain Sciences, MC-9660, University of California Santa Barbara, Santa Barbara, CA 93106-9660, United States of America., Wroten MG; Department of Psychological and Brain Sciences, MC-9660, University of California Santa Barbara, Santa Barbara, CA 93106-9660, United States of America., Sacramento A; Department of Psychological and Brain Sciences, MC-9660, University of California Santa Barbara, Santa Barbara, CA 93106-9660, United States of America., Travis KO; Department of Psychological and Brain Sciences, MC-9660, University of California Santa Barbara, Santa Barbara, CA 93106-9660, United States of America., Kippin TE; Department of Psychological and Brain Sciences, MC-9660, University of California Santa Barbara, Santa Barbara, CA 93106-9660, United States of America; Department of Molecular, Cellular and Developmental Biology and the Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93106, United States of America., Ben-Shahar O; Department of Psychological and Brain Sciences, MC-9660, University of California Santa Barbara, Santa Barbara, CA 93106-9660, United States of America., Szumlinski KK; Department of Psychological and Brain Sciences, MC-9660, University of California Santa Barbara, Santa Barbara, CA 93106-9660, United States of America; Department of Molecular, Cellular and Developmental Biology and the Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA 93106, United States of America. Electronic address: szumlinski@ucsb.edu.
Jazyk: angličtina
Zdroj: Pharmacology, biochemistry, and behavior [Pharmacol Biochem Behav] 2024 Dec; Vol. 245, pp. 173889. Date of Electronic Publication: 2024 Oct 09.
DOI: 10.1016/j.pbb.2024.173889
Abstrakt: Cue-elicited drug-seeking behavior intensifies with the passage of time during withdrawal from drug taking and this "incubation of cocaine-craving" involves alterations in nucleus accumbens (NA) glutamate transmission. Here, we employed a combination of in vivo microdialysis and immunoblotting approaches to further examine changes in biochemical indices of glutamate transmission within NA subregions that accompany the incubation of cocaine-craving exhibited by male rats with a 10-day history of 6-h access to intravenous cocaine (0.25 mg/infusion). Immunoblotting on whole cell lysates from the core subregion (NAc core) revealed interactions between cocaine self-administration history, withdrawal and drug cue re-exposure for Homer2a/b, mGlu1, and GluN2b expression, as well as indices of Akt and ERK activity. With the exception of PKCε phosphorylation, most protein changes within the shell subregion (NAc shell) depended on drug cue re-exposure and cocaine history rather than varying in a consistent time-dependent manner. Reduced basal extracellular glutamate content was apparent only in the NAc core of cocaine-experienced rats during protracted (30 days) withdrawal and this was accompanied by a markedly blunted capacity of the mGlu1/5 agonist DHPG to elevate glutamate levels within this subregion. Finally, over-expressing neither Homer1c nor Homer2b within the NAc core during protracted cocaine withdrawal altered the magnitude of cue-elicited responding, its extinction or cocaine-primed reinstatement of drug-seeking behavior. The present findings are consistent with the extant literature implicating changes in Group 1 mGlu receptor function within the NAc core subregion as central to incubated cocaine-craving and provide further evidence against a major role for Homer proteins in gating incubated cocaine-craving. Further, our results provide novel correlational evidence implicating elevated Akt and blunted ERK activity within the NAc core as potential contributors to the expression of incubated cocaine-craving, worthy of future investigation.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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