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Dependence-induced ethanol drinking and GABA neurotransmission are altered in Alk deficient mice.
Neuropharmacology. 2016 08; 107:1-8.N

Abstract

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is expressed in the brain and implicated in alcohol abuse in humans and behavioral responses to ethanol in mice. Previous studies have shown an association of human ALK with acute responses to alcohol and alcohol dependence. In addition, Alk knockout (Alk -/-) mice consume more ethanol in a binge-drinking test and show increased sensitivity to ethanol sedation. However, the function of ALK in excessive drinking following the establishment of ethanol dependence has not been examined. In this study, we tested Alk -/- mice for dependence-induced drinking using the chronic intermittent ethanol-two bottle choice drinking (CIE-2BC) protocol. We found that Alk -/- mice initially consume more ethanol prior to CIE exposure, but do not escalate ethanol consumption after exposure, suggesting that ALK may promote the escalation of drinking after ethanol dependence. To determine the mechanism(s) responsible for this behavioral phenotype we used an electrophysiological approach to examine GABA neurotransmission in the central nucleus of the amygdala (CeA), a brain region that regulates alcohol consumption and shows increased GABA signaling after chronic ethanol exposure. GABA transmission in ethanol-naïve Alk -/- mice was enhanced at baseline and potentiated in response to acute ethanol application when compared to wild-type (Alk +/+) mice. Moreover, basal GABA transmission was not elevated by CIE exposure in Alk -/- mice as it was in Alk +/+ mice. These data suggest that ALK plays a role in dependence-induced drinking and the regulation of presynaptic GABA release in the CeA.

Authors+Show Affiliations

Committee on the Neurobiology of Addictive Disorders, SP30-2400, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.Department of Molecular and Cellular Neuroscience, MB-18, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.Committee on the Neurobiology of Addictive Disorders, SP30-2400, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.Department of Molecular and Cellular Neuroscience, MB-18, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.Committee on the Neurobiology of Addictive Disorders, SP30-2400, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.Department of Psychiatry, University of Illinois at Chicago, 1601 West Taylor Street, M/C 912, Chicago, IL 60612, USA. Electronic address: alasek@psych.uic.edu.Department of Molecular and Cellular Neuroscience, MB-18, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26946429

Citation

Schweitzer, Paul, et al. "Dependence-induced Ethanol Drinking and GABA Neurotransmission Are Altered in Alk Deficient Mice." Neuropharmacology, vol. 107, 2016, pp. 1-8.
Schweitzer P, Cates-Gatto C, Varodayan FP, et al. Dependence-induced ethanol drinking and GABA neurotransmission are altered in Alk deficient mice. Neuropharmacology. 2016;107:1-8.
Schweitzer, P., Cates-Gatto, C., Varodayan, F. P., Nadav, T., Roberto, M., Lasek, A. W., & Roberts, A. J. (2016). Dependence-induced ethanol drinking and GABA neurotransmission are altered in Alk deficient mice. Neuropharmacology, 107, 1-8. https://doi.org/10.1016/j.neuropharm.2016.03.003
Schweitzer P, et al. Dependence-induced Ethanol Drinking and GABA Neurotransmission Are Altered in Alk Deficient Mice. Neuropharmacology. 2016;107:1-8. PubMed PMID: 26946429.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dependence-induced ethanol drinking and GABA neurotransmission are altered in Alk deficient mice. AU - Schweitzer,Paul, AU - Cates-Gatto,Chelsea, AU - Varodayan,Florence P, AU - Nadav,Tali, AU - Roberto,Marisa, AU - Lasek,Amy W, AU - Roberts,Amanda J, Y1 - 2016/03/02/ PY - 2015/11/12/received PY - 2016/02/05/revised PY - 2016/03/01/accepted PY - 2016/3/7/entrez PY - 2016/3/8/pubmed PY - 2017/6/22/medline KW - ALK KW - Addiction KW - Amygdala KW - Chronic intermittent ethanol KW - GABA KW - Synaptic SP - 1 EP - 8 JF - Neuropharmacology JO - Neuropharmacology VL - 107 N2 - Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is expressed in the brain and implicated in alcohol abuse in humans and behavioral responses to ethanol in mice. Previous studies have shown an association of human ALK with acute responses to alcohol and alcohol dependence. In addition, Alk knockout (Alk -/-) mice consume more ethanol in a binge-drinking test and show increased sensitivity to ethanol sedation. However, the function of ALK in excessive drinking following the establishment of ethanol dependence has not been examined. In this study, we tested Alk -/- mice for dependence-induced drinking using the chronic intermittent ethanol-two bottle choice drinking (CIE-2BC) protocol. We found that Alk -/- mice initially consume more ethanol prior to CIE exposure, but do not escalate ethanol consumption after exposure, suggesting that ALK may promote the escalation of drinking after ethanol dependence. To determine the mechanism(s) responsible for this behavioral phenotype we used an electrophysiological approach to examine GABA neurotransmission in the central nucleus of the amygdala (CeA), a brain region that regulates alcohol consumption and shows increased GABA signaling after chronic ethanol exposure. GABA transmission in ethanol-naïve Alk -/- mice was enhanced at baseline and potentiated in response to acute ethanol application when compared to wild-type (Alk +/+) mice. Moreover, basal GABA transmission was not elevated by CIE exposure in Alk -/- mice as it was in Alk +/+ mice. These data suggest that ALK plays a role in dependence-induced drinking and the regulation of presynaptic GABA release in the CeA. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/26946429/Dependence_induced_ethanol_drinking_and_GABA_neurotransmission_are_altered_in_Alk_deficient_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(16)30076-4 DB - PRIME DP - Unbound Medicine ER -