Corticotropin Releasing Factor Binding Protein and CRF2 Receptors in the Ventral Tegmental Area: Modulation of Ethanol Binge Drinking in C57BL/6J Mice. (6th August 2015)

• Record Type: Journal Article
• Authors: Albrechet‐Souza, Lucas; Hwa, Lara S.; Han, Xiao; Zhang, Eric Y.; DeBold, Joseph F.; Miczek, Klaus A.
• Is Part Of: Alcoholism. Volume 39:Number 9(2015:Sep.)
• Page Start: 1609
• Page End: 1618
• Publication Date: 2015-08-06
• Subjects: Alcoholism -- Periodicals; Alcoholism -- Periodicals; Alcoolisme; Electronic journals; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.861005
• DOI: 10.1111/acer.12825
• Languages: English
• ISSNs: 0145-6008

Abstract

<abstract abstract-type="main" id="acer12825-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="acer12825-sec-0001" sec-type="section"> <title>Background</title> <p>Most studies with corticotropin releasing factor (CRF) and ethanol (EtOH) consumption have focused on CRF type 1 (CRF<sub>1</sub>) receptors; less is known about other components of the CRF system, such as the CRF type 2 (CRF<sub>2</sub>) receptors and the CRF binding protein (CRFBP). In humans, several nucleotide polymorphisms in the <italic>CRFBP</italic> gene have been associated with EtOH abuse.</p> </sec> <sec id="acer12825-sec-0002" sec-type="section"> <title>Methods</title> <p>The role of the CRFBP within the ventral tegmental area (VTA) and the central nucleus of the amygdala (CeA) was investigated in C57BL/6J mice exposed to an EtOH binge drinking paradigm (drinking in the dark [DID]), or to a dependence‐producing drinking protocol (2‐bottle choice, intermittent access to alcohol [IAA]) for 4 weeks. Potential interactions between VTA CRFBP and CRF<sub>2</sub> receptors on EtOH binge drinking were also assessed. Mice were microinjected with the CRFBP antagonist CRF fragment 6–33 (CRF<sub>6–33</sub>) into the VTA or CeA, or with the CRF<sub>2</sub> antagonist astressin‐2B (A2B) alone or in combination with CRF<sub>6–33</sub> into the VTA, and had access to 20% (w/v) EtOH for 4 hours (DID). Separate cohorts of mice received vehicle and doses of CRF<sub>6–33</sub> into the VTA or CeA and had access to EtOH/water for 24 hours (IAA). Blood EtOH concentrations (BECs) were measured, and signs of withdrawal by handling‐induced convulsions were determined.</p> </sec> <sec id="acer12825-sec-0003" sec-type="section"> <title>Results</title> <p>Intra‐VTA CRF<sub>6–33</sub> and A2B reduced EtOH intake dose dependently in mice during DID. Furthermore, a combination of a subeffective dose of CRF<sub>6–33</sub> and a lower dose of A2B promoted additive effects in attenuating EtOH binge drinking. Intra‐VTA CRF<sub>6–33</sub> did not affect EtOH consumption in mice given IAA, and intra‐CeA CRF<sub>6–33</sub> did not change alcohol consumption in both models of drinking. DID and IAA promoted pharmacologically relevant BECs; however, only mice given IAA exhibited convulsive events during withdrawal.</p> </sec> <sec id="acer12825-sec-0004" sec-type="section"> <title>Conclusions</title> <p>These findings suggest that VTA CRFBP is involved in the initial stages of escalated EtOH drinking by mechanisms that may involve CRF<sub>2</sub> receptors.</p> </sec> </abstract>