Prefrontal cortex glutamatergic adaptations in a mouse model of alcohol use disorder.

Autor:	Siddiqi MT; Developmental Exposure Alcohol Research Center and Behavioral Neuroscience Program, Department of Psychology, Binghamton University-SUNY, 4400 Vestal Parkway East, Binghamton, NY, 13902, USA., Podder D; Developmental Exposure Alcohol Research Center and Behavioral Neuroscience Program, Department of Psychology, Binghamton University-SUNY, 4400 Vestal Parkway East, Binghamton, NY, 13902, USA., Pahng AR; Department of Physiology, Louisiana State University Health Sciences Center, 533 Bolivar Street, New Orleans, LA, 70112, USA.; Southeast Louisiana Veterans Health Care System, 2400 Canal Street, 11F, New Orleans, LA, 70119, USA., Athanason AC; Developmental Exposure Alcohol Research Center and Behavioral Neuroscience Program, Department of Psychology, Binghamton University-SUNY, 4400 Vestal Parkway East, Binghamton, NY, 13902, USA., Nadav T; Animal Models Core Facility, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA., Cates-Gatto C; Animal Models Core Facility, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA., Kreifeldt M; Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA., Contet C; Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA., Roberts AJ; Animal Models Core Facility, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA., Edwards S; Department of Physiology, Louisiana State University Health Sciences Center, 533 Bolivar Street, New Orleans, LA, 70112, USA., Roberto M; Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA., Varodayan FP; Developmental Exposure Alcohol Research Center and Behavioral Neuroscience Program, Department of Psychology, Binghamton University-SUNY, 4400 Vestal Parkway East, Binghamton, NY, 13902, USA.; Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
Jazyk:	angličtina
Zdroj:	Addiction neuroscience [Addict Neurosci] 2023 Dec 15; Vol. 9. Date of Electronic Publication: 2023 Nov 14.
DOI:	10.1016/j.addicn.2023.100137
Abstrakt:	Alcohol use disorder (AUD) produces cognitive deficits, indicating a shift in prefrontal cortex (PFC) function. PFC glutamate neurotransmission is mostly mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type ionotropic receptors (AMPARs); however preclinical studies have mostly focused on other receptor subtypes. Here we examined the impact of early withdrawal from chronic ethanol on AMPAR function in the mouse medial PFC (mPFC). Dependent male C57BL/6J mice were generated using the chronic intermittent ethanol vapor-two bottle choice (CIE-2BC) paradigm. Non-dependent mice had access to water and ethanol bottles but did not receive ethanol vapor. Naïve mice had no ethanol exposure. We used patch-clamp electrophysiology to measure glutamate neurotransmission in layer 2/3 prelimbic mPFC pyramidal neurons. Since AMPAR function can be impacted by subunit composition or plasticity-related proteins, we probed their mPFC expression levels. Dependent mice had higher spontaneous excitatory postsynaptic current (sEPSC) amplitude and kinetics compared to the Naïve/Non-dependent mice. These effects were seen during intoxication and after 3-8 days withdrawal, and were action potential-independent, suggesting direct enhancement of AMPAR function. Surprisingly, 3 days withdrawal decreased expression of genes encoding AMPAR subunits ( Gria1/2 ) and synaptic plasticity proteins ( Dlg4 and Grip1 ) in Dependent mice. Further analysis within the Dependent group revealed a negative correlation between Gria1 mRNA levels and ethanol intake. Collectively, these data establish a role for mPFC AMPAR adaptations in the glutamatergic dysfunction associated with ethanol dependence. Future studies on the underlying AMPAR plasticity mechanisms that promote alcohol reinforcement, seeking, drinking and relapse behavior may help identify new targets for AUD treatment. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Databáze:	MEDLINE
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