Journal article
Intoxicating effects of alcohol depend on acid-sensing ion channels
Neuropsychopharmacology (New York, N.Y.), Vol.48(5), pp.806-815
04/2023
DOI: 10.1038/s41386-022-01473-4
PMCID: PMC10066229
PMID: 36243771
Abstract
Persons at risk for developing alcohol use disorder (AUD) differ in their sensitivity to acute alcohol intoxication. Alcohol effects are complex and thought to depend on multiple mechanisms. Here, we explored whether acid-sensing ion channels (ASICs) might play a role. We tested ASIC function in transfected CHO cells and amygdala principal neurons, and found alcohol potentiated currents mediated by ASIC1A homomeric channels, but not ASIC1A/2 A heteromeric channels. Supporting a role for ASIC1A in the intoxicating effects of alcohol in vivo, we observed marked alcohol-induced changes on local field potentials in basolateral amygdala, which differed significantly in Asic1a–/– mice, particularly in the gamma, delta, and theta frequency ranges. Altered electrophysiological responses to alcohol in mice lacking ASIC1A, were accompanied by changes in multiple behavioral measures. Alcohol administration during amygdala-dependent fear conditioning dramatically diminished context and cue-evoked memory on subsequent days after the alcohol had cleared. There was a significant alcohol by genotype interaction. Context- and cue-evoked memory were notably worse in Asic1a–/– mice. We further examined acute stimulating and sedating effects of alcohol on locomotor activity, loss of righting reflex, and in an acute intoxication severity scale. We found loss of ASIC1A increased the stimulating effects of alcohol and reduced the sedating effects compared to wild-type mice, despite similar blood alcohol levels. Together these observations suggest a novel role for ASIC1A in the acute intoxicating effects of alcohol in mice. They further suggest that ASICs might contribute to intoxicating effects of alcohol and AUD in humans.
Details
- Title: Subtitle
- Intoxicating effects of alcohol depend on acid-sensing ion channels
- Creators
- Gail I S Harmata - University of IowaAubrey C ChanMadison J MerfeldRebecca J Taugher-HeblAnjit K HarijanJason B HardieRong FanJeffrey D LongGrace Z WangBrian J DlouhyAmal K BeraNandakumar S NarayananJohn A Wemmie
- Resource Type
- Journal article
- Publication Details
- Neuropsychopharmacology (New York, N.Y.), Vol.48(5), pp.806-815
- DOI
- 10.1038/s41386-022-01473-4
- PMID
- 36243771
- PMCID
- PMC10066229
- NLM abbreviation
- Neuropsychopharmacology
- ISSN
- 0893-133X
- eISSN
- 1740-634X
- Grant note
- DOI: 10.13039/100000065, name: U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke, award: T32NS007421, NS-112573; DOI: 10.13039/100000057, name: U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences, award: T32GM067795; name: University of Iowa Ballard and Seashore Dissertation Fellowship; DOI: 10.13039/100000025, name: U.S. Department of Health & Human Services | NIH | National Institute of Mental Health, award: T32MH019113, R01MH116043-01A1, R01MH113325; name: Iowa Neuroscience Institute Summer Scholar Award; DOI: 10.13039/501100010426, name: University Grants Commission India | UGC-DAE Consortium for Scientific Research, University Grants Commission, award: unknown; name: U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke; name: U.S. Department of Health & Human Services | NIH | National Institute of Mental Health; name: U.S. Department of Health & Human Services | NIH | National Institute of Mental Health; DOI: 10.13039/100000026, name: U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse, award: R01DA052953; name: Roy J. Carver Charitable Trust Roy J. Carver Chair U.S. Department of Veterans Affairs Merit Review Award U.S. Department of Veterans Affairs
- Language
- English
- Electronic publication date
- 10/15/2022
- Date published
- 04/2023
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Biostatistics; Biology; Neurosurgery; Internal Medicine
- Record Identifier
- 9984305989602771
Metrics
15 Record Views