Adolescent Ethanol Exposure Enhances NMDA Receptor-Mediated Currents in Hippocampal Neurons: Reversal by Gabapentin
Open accessAbstract
Adolescent intermittent ethanol (AIE) exposure compromises neural function into adulthood. We have reported that astrocyte-secreted thrombospondins, and their target neuronal receptors (α2δ−1) are upregulated in the hippocampus in adulthood after AIE, suggesting aberrant excitatory synaptogenesis and hyperexcitability in memory-related circuits. Gabapentin antagonizes the interaction of thrombospondins (TSPs) with the α2δ−1 receptor, and thus may reverse or ameliorate the effects of AIE on hippocampal function. Adolescent rats were exposed to AIE or vehicle. In adulthood, hippocampal slices were prepared. Half of the slices from each animal were pre-incubated in normal artificial cerebrospinal fluid (aCSF) while half were pre-incubated in aCSF containing gabapentin. Whole-cell voltage clamp recordings were then made from CA1 pyramidal cells in normal aCSF. Evoked, N-methyl-D-aspartate (NMDA) receptor-mediated currents were recorded at baseline, and after application of the GluN2B antagonist, RO25–6981. Current amplitudes were higher in neurons from AIE-exposed animals. However, no amplitude increase was observed in neurons from slices that had been pre-incubation in gabapentin. GluN2B antagonism reduced NMDA receptor-mediated currents more efficaciously in cells from AIE-exposed animals, an effect that was also reversed by pre-incubation in gabapentin. These findings identify a mechanism underlying the enduring effects of AIE, and a clinically-utilized agent that may ameliorate those effects.
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Evidence suggests adolescent alcohol exposure alters glutamatergic function, and increases in hippocampal glutamate have been linked to schizophrenia and psychosis.
“This finding is particularly relevant given the evidence suggesting AAE alters glutamatergic function [73, 74], and increases in hippocampal glutamate have been linked to schizophrenia [75] and psychosis [76].”
From Consequences of adolescent drug use (2023) · cites this paper as [74]
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- Authors
- Swartzwelder, H. S., Park, M.-H., & Acheson, S.
- Affiliations
- Duke University (US)
- Corresponding author
- Swartzwelder, H. S.
- Venue
- Scientific Reports
- Published
- 2017-10-13
- Volume
- 7
- Issue
- 1
- Pages
- 13133-13133
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5640643
- OpenAlex
- W2762528733
- Cited by
- 38
- References
- 28
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 1 · 2023: 8 · 2022: 4 · 2021: 5 · 2020: 9 · 2019: 4 · 2018: 2
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Institutes of Health
- National Institute on Alcohol Abuse and Alcoholism (U01AA019925)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
- Keywords
- adolescent intermittent ethanol exposure, NMDA receptor currents, gabapentin, GluN2B, CA1 pyramidal neurons, thrombospondin, neuronal hyperexcitability, neuroprotection
- MeSH terms
- Gabapentin, Ethanol, Animals, Electrophysiology, Hippocampus, Male, Neurons, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Thrombospondins, Rats
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