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Effect of Gabapentin on Sleep and Event-Related Oscillations (EROs) in Rats Exposed to Chronic Intermittent Ethanol Vapor and Protracted Withdrawal.
Alcohol Clin Exp Res. 2018 Mar; 42(3):624-633.AC

Abstract

BACKGROUND

Disturbances in sleep architecture, especially reductions in slow-wave sleep (SWS), are symptoms commonly observed in individuals with alcohol use disorders. Recent clinical trials have demonstrated that the anticonvulsant and analgesic drug gabapentin may have therapeutic value in normalizing sleep quality in recovering alcoholics. However, the brain mechanisms underlying this improvement in sleep following gabapentin treatment remain unknown.

METHODS

In this study, adult Wistar rats were exposed to 8 weeks of chronic intermittent ethanol [EtOH] vapor (blood EtOH concentrations averaged 128.2 ± 17.4 mg/dl) or control conditions and then withdrawn. Sleep electroencephalograms [EEGs] and event-related oscillations (EROs) were evaluated at baseline prior to EtOH exposure and 24 hours following EtOH withdrawal. Four weeks following EtOH withdrawal the effects of saline and 2 doses of gabapentin (30, 120 mg/kg), on EROs and sleep EEGs, were evaluated.

RESULTS

As compared to baseline, 24 hours following alcohol withdrawal SWS became fragmented as indexed by a significant increase in the number and a decrease in the duration of SWS episodes. Compared to controls, the EtOH-exposed group had more ERO energy in the beta frequency band in the parietal cortex. Gabapentin induced a dose-dependent decrease in the latency to the first SWS episode, and a reduction in sleep fragmentation. Gabapentin also produced a dose-dependent increase in ERO energy in the control group that was significantly attenuated in the EtOH-exposed group in the theta, and beta frequency bands.

CONCLUSIONS

Taken together, these studies suggest that gabapentin can reverse some of the alcohol-induced sleep and EEG deficits but does not eliminate all of the enduring brain effects of EtOH exposure.

Authors+Show Affiliations

Department of Neurosciences, The Scripps Research Institute, La Jolla, California.Department of Neurosciences, The Scripps Research Institute, La Jolla, California.Department of Neurosciences, The Scripps Research Institute, La Jolla, California.Department of Neurosciences, The Scripps Research Institute, La Jolla, California.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

29286538

Citation

Sanchez-Alavez, Manuel, et al. "Effect of Gabapentin On Sleep and Event-Related Oscillations (EROs) in Rats Exposed to Chronic Intermittent Ethanol Vapor and Protracted Withdrawal." Alcoholism, Clinical and Experimental Research, vol. 42, no. 3, 2018, pp. 624-633.
Sanchez-Alavez M, Wills DN, Amodeo L, et al. Effect of Gabapentin on Sleep and Event-Related Oscillations (EROs) in Rats Exposed to Chronic Intermittent Ethanol Vapor and Protracted Withdrawal. Alcohol Clin Exp Res. 2018;42(3):624-633.
Sanchez-Alavez, M., Wills, D. N., Amodeo, L., & Ehlers, C. L. (2018). Effect of Gabapentin on Sleep and Event-Related Oscillations (EROs) in Rats Exposed to Chronic Intermittent Ethanol Vapor and Protracted Withdrawal. Alcoholism, Clinical and Experimental Research, 42(3), 624-633. https://doi.org/10.1111/acer.13588
Sanchez-Alavez M, et al. Effect of Gabapentin On Sleep and Event-Related Oscillations (EROs) in Rats Exposed to Chronic Intermittent Ethanol Vapor and Protracted Withdrawal. Alcohol Clin Exp Res. 2018;42(3):624-633. PubMed PMID: 29286538.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of Gabapentin on Sleep and Event-Related Oscillations (EROs) in Rats Exposed to Chronic Intermittent Ethanol Vapor and Protracted Withdrawal. AU - Sanchez-Alavez,Manuel, AU - Wills,Derek N, AU - Amodeo,Leslie, AU - Ehlers,Cindy L, Y1 - 2018/01/31/ PY - 2017/09/28/received PY - 2017/12/20/accepted PY - 2017/12/30/pubmed PY - 2019/9/19/medline PY - 2017/12/30/entrez KW - Alcohol KW - EEG KW - Event-Related Oscillations KW - Gabapentin KW - Slow-Wave Sleep SP - 624 EP - 633 JF - Alcoholism, clinical and experimental research JO - Alcohol. Clin. Exp. Res. VL - 42 IS - 3 N2 - BACKGROUND: Disturbances in sleep architecture, especially reductions in slow-wave sleep (SWS), are symptoms commonly observed in individuals with alcohol use disorders. Recent clinical trials have demonstrated that the anticonvulsant and analgesic drug gabapentin may have therapeutic value in normalizing sleep quality in recovering alcoholics. However, the brain mechanisms underlying this improvement in sleep following gabapentin treatment remain unknown. METHODS: In this study, adult Wistar rats were exposed to 8 weeks of chronic intermittent ethanol [EtOH] vapor (blood EtOH concentrations averaged 128.2 ± 17.4 mg/dl) or control conditions and then withdrawn. Sleep electroencephalograms [EEGs] and event-related oscillations (EROs) were evaluated at baseline prior to EtOH exposure and 24 hours following EtOH withdrawal. Four weeks following EtOH withdrawal the effects of saline and 2 doses of gabapentin (30, 120 mg/kg), on EROs and sleep EEGs, were evaluated. RESULTS: As compared to baseline, 24 hours following alcohol withdrawal SWS became fragmented as indexed by a significant increase in the number and a decrease in the duration of SWS episodes. Compared to controls, the EtOH-exposed group had more ERO energy in the beta frequency band in the parietal cortex. Gabapentin induced a dose-dependent decrease in the latency to the first SWS episode, and a reduction in sleep fragmentation. Gabapentin also produced a dose-dependent increase in ERO energy in the control group that was significantly attenuated in the EtOH-exposed group in the theta, and beta frequency bands. CONCLUSIONS: Taken together, these studies suggest that gabapentin can reverse some of the alcohol-induced sleep and EEG deficits but does not eliminate all of the enduring brain effects of EtOH exposure. SN - 1530-0277 UR - https://www.unboundmedicine.com/medline/citation/29286538/Effect_of_Gabapentin_on_Sleep_and_Event_Related_Oscillations__EROs__in_Rats_Exposed_to_Chronic_Intermittent_Ethanol_Vapor_and_Protracted_Withdrawal_ L2 - https://doi.org/10.1111/acer.13588 DB - PRIME DP - Unbound Medicine ER -