Dependence-induced ethanol drinking and GABA neurotransmission are altered in Alk deficient mice. (August 2016)

• Record Type: Journal Article
• Authors: Schweitzer, Paul; Cates-Gatto, Chelsea; Varodayan, Florence P.; Nadav, Tali; Roberto, Marisa; Lasek, Amy W.; Roberts, Amanda J.
• Is Part Of: Neuropharmacology. Volume 107(2016)
• Page Start: 1
• Page End: 8
• Publication Date: 2016-08
• Subjects: Addiction -- ALK -- Amygdala -- Chronic intermittent ethanol -- GABA -- Synaptic; ALK anaplastic lymphoma kinase -- CeA central nucleus of the amygdala -- CIE chronic intermittent ethanol -- ERK extracellular signal-regulated kinase -- GABA gamma amino-butyric acid -- sIPSCs spontaneous inhibitory post-synaptic currents -- 2BC two bottle choice; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2016.03.003
• Languages: English
• ISSNs: 0028-3908

Abstract

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. Highlights: Mice deficient in the Alk gene consume more ethanol than controls. Alk deficient mice exhibit enhanced basal GABA release in the amygdala. Ethanol-potentiated GABA release is higher in Alk deficient mice. Alk deficient mice do not escalate ethanol drinking after chronic ethanol exposure. GABA release does not increase after chronic ethanol exposure in Alk deficient mice.