Effects of Withdrawal from Cocaine Self-Administration on Rat Orbitofrontal Cortex Parvalbumin Neurons Expressing Cre recombinase : Sex-Dependent Changes in Neuronal Function and Unaltered Serotonin Signaling.

Autor: Wright AM; Electrophysiology Research Section, Cellular Neurobiology Branch with: Cellular and Neurocomputational Systems Branch., Zapata A; Electrophysiology Research Section, Cellular Neurobiology Branch with: Cellular and Neurocomputational Systems Branch., Hoffman AF; Electrophysiology Research Section, Cellular Neurobiology Branch with: Cellular and Neurocomputational Systems Branch., Necarsulmer JC; Molecular Mechanisms of Cellular Stress and Inflammation Section.; Optogenetics and Transgenic Technology Core., Coke LM; Molecular Mechanisms of Cellular Stress and Inflammation Section.; Optogenetics and Transgenic Technology Core., Svarcbahs R; Molecular Mechanisms of Cellular Stress and Inflammation Section.; Optogenetics and Transgenic Technology Core., Richie CT; Optogenetics and Transgenic Technology Core., Pickel J; Transgenic Technology Core, Intramural Research Program, National Institute of Mental Health, Bethesda, MD 20892., Hope BT; Neuronal Ensembles in Drug Addiction Section Integrative Neuroscience Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224., Harvey BK; Molecular Mechanisms of Cellular Stress and Inflammation Section.; Optogenetics and Transgenic Technology Core., Lupica CR; Electrophysiology Research Section, Cellular Neurobiology Branch with: Cellular and Neurocomputational Systems Branch clupica@nih.gov.
Jazyk: angličtina
Zdroj: ENeuro [eNeuro] 2021 Jul 08; Vol. 8 (4). Date of Electronic Publication: 2021 Jul 08 (Print Publication: 2021).
DOI: 10.1523/ENEURO.0017-21.2021
Abstrakt: The orbitofrontal cortex (OFC) is a brain region involved in higher-order decision-making. Rodent studies show that cocaine self-administration (CSA) reduces OFC contribution to goal-directed behavior and behavioral strategies to avoid drug intake. This change in OFC function persists for many weeks after cocaine withdrawal, suggesting involvement in the process of addiction. The mechanisms underlying impaired OFC function by cocaine are not well-understood. However, studies implicate altered OFC serotonin (5-HT) function in disrupted cognitive processes during addiction and other psychiatric disorders. Thus, it is hypothesized that cocaine impairment of OFC function involves changes in 5-HT signaling, and previous work shows that 5-HT 1A and 5-HT 2A receptor-mediated effects on OFC pyramidal neurons (PyNs) are impaired weeks after cocaine withdrawal. However, 5-HT effects on other contributors to OFC circuit function have not been fully investigated, including the parvalbumin-containing, fast-spiking interneurons (OFC PV ), whose function is essential to normal OFC-mediated behavior. Here, 5-HT function in naive rats and those withdrawn from CSA were evaluated using a novel rat transgenic line in which the rat parvalbumin promoter drives Cre-recombinase expression to permit identification of OFC PV cells by fluorescent reporter protein expression. We find that whereas CSA altered basal synaptic and membrane properties of the OFC PV neurons in a sex-dependent manner, the effects of 5-HT on these cells were unchanged by CSA. These data suggest that the behavioral effects of dysregulated OFC 5-HT function caused by cocaine experience are primarily mediated by changes in 5-HT signaling at PyNs, and not at OFC PV neurons.
(Copyright © 2021 Wright et al.)
Databáze: MEDLINE
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