Prefrontal cortex glutamatergic adaptations in a mouse model of alcohol use disorder
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 focus...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-12-01
|
| Series: | Addiction Neuroscience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772392523000809 |
| _version_ | 1797390323439108096 |
|---|---|
| author | Mahum T. Siddiqi Dhruba Podder Amanda R. Pahng Alexandria C. Athanason Tali Nadav Chelsea Cates-Gatto Max Kreifeldt Candice Contet Amanda J. Roberts Scott Edwards Marisa Roberto Florence P. Varodayan |
| author_facet | Mahum T. Siddiqi Dhruba Podder Amanda R. Pahng Alexandria C. Athanason Tali Nadav Chelsea Cates-Gatto Max Kreifeldt Candice Contet Amanda J. Roberts Scott Edwards Marisa Roberto Florence P. Varodayan |
| author_sort | Mahum T. Siddiqi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T23:09:05Z |
| format | Article |
| id | doaj.art-06eb8a910c9d45f59ac89c917ba77f9d |
| institution | Directory Open Access Journal |
| issn | 2772-3925 |
| language | English |
| last_indexed | 2024-03-08T23:09:05Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Addiction Neuroscience |
| spelling | doaj.art-06eb8a910c9d45f59ac89c917ba77f9d2023-12-15T07:27:20ZengElsevierAddiction Neuroscience2772-39252023-12-019100137Prefrontal cortex glutamatergic adaptations in a mouse model of alcohol use disorderMahum T. Siddiqi0Dhruba Podder1Amanda R. Pahng2Alexandria C. Athanason3Tali Nadav4Chelsea Cates-Gatto5Max Kreifeldt6Candice Contet7Amanda J. Roberts8Scott Edwards9Marisa Roberto10Florence P. Varodayan11Developmental Exposure Alcohol Research Center and Behavioral Neuroscience Program, Department of Psychology, Binghamton University-SUNY, 4400 Vestal Parkway East, Binghamton, NY, 13902, USADevelopmental Exposure Alcohol Research Center and Behavioral Neuroscience Program, Department of Psychology, Binghamton University-SUNY, 4400 Vestal Parkway East, Binghamton, NY, 13902, USADepartment 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, USADevelopmental Exposure Alcohol Research Center and Behavioral Neuroscience Program, Department of Psychology, Binghamton University-SUNY, 4400 Vestal Parkway East, Binghamton, NY, 13902, USAAnimal Models Core Facility, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USAAnimal Models Core Facility, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USADepartment of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USADepartment of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USAAnimal Models Core Facility, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USADepartment of Physiology, Louisiana State University Health Sciences Center, 533 Bolivar Street, New Orleans, LA, 70112, USADepartment of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USADevelopmental 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; Corresponding author at: Department of Psychology, Binghamton University-SUNY, S4-175G, 4400 Vestal Parkway East, Binghamton, NY 13902, USA.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.http://www.sciencedirect.com/science/article/pii/S2772392523000809AddictionAMPAGluR1NeuroplasticityExcitatory transmission |
| spellingShingle | Mahum T. Siddiqi Dhruba Podder Amanda R. Pahng Alexandria C. Athanason Tali Nadav Chelsea Cates-Gatto Max Kreifeldt Candice Contet Amanda J. Roberts Scott Edwards Marisa Roberto Florence P. Varodayan Prefrontal cortex glutamatergic adaptations in a mouse model of alcohol use disorder Addiction Neuroscience Addiction AMPA GluR1 Neuroplasticity Excitatory transmission |
| title | Prefrontal cortex glutamatergic adaptations in a mouse model of alcohol use disorder |
| title_full | Prefrontal cortex glutamatergic adaptations in a mouse model of alcohol use disorder |
| title_fullStr | Prefrontal cortex glutamatergic adaptations in a mouse model of alcohol use disorder |
| title_full_unstemmed | Prefrontal cortex glutamatergic adaptations in a mouse model of alcohol use disorder |
| title_short | Prefrontal cortex glutamatergic adaptations in a mouse model of alcohol use disorder |
| title_sort | prefrontal cortex glutamatergic adaptations in a mouse model of alcohol use disorder |
| topic | Addiction AMPA GluR1 Neuroplasticity Excitatory transmission |
| url | http://www.sciencedirect.com/science/article/pii/S2772392523000809 |
| work_keys_str_mv | AT mahumtsiddiqi prefrontalcortexglutamatergicadaptationsinamousemodelofalcoholusedisorder AT dhrubapodder prefrontalcortexglutamatergicadaptationsinamousemodelofalcoholusedisorder AT amandarpahng prefrontalcortexglutamatergicadaptationsinamousemodelofalcoholusedisorder AT alexandriacathanason prefrontalcortexglutamatergicadaptationsinamousemodelofalcoholusedisorder AT talinadav prefrontalcortexglutamatergicadaptationsinamousemodelofalcoholusedisorder AT chelseacatesgatto prefrontalcortexglutamatergicadaptationsinamousemodelofalcoholusedisorder AT maxkreifeldt prefrontalcortexglutamatergicadaptationsinamousemodelofalcoholusedisorder AT candicecontet prefrontalcortexglutamatergicadaptationsinamousemodelofalcoholusedisorder AT amandajroberts prefrontalcortexglutamatergicadaptationsinamousemodelofalcoholusedisorder AT scottedwards prefrontalcortexglutamatergicadaptationsinamousemodelofalcoholusedisorder AT marisaroberto prefrontalcortexglutamatergicadaptationsinamousemodelofalcoholusedisorder AT florencepvarodayan prefrontalcortexglutamatergicadaptationsinamousemodelofalcoholusedisorder |