title: Novel subunit-specific tonic GABA currents and differential effects of ethanol in the central amygdala of CRF receptor-1 reporter mice.
abstract: The central nucleus of the amygdala (CeA) is an important integrative site for the reinforcing effects of drugs of abuse, such as ethanol. Activation of corticotropin-releasing factor type 1 (CRF1) receptors in the CeA plays a critical role in the development of ethanol dependence, but these neurons remain uncharacterized. Using CRF1:GFP reporter mice and a combined electrophysiological/immunohistochemical approach, we found that CRF1 neurons exhibit an α1 GABA(A) receptor subunit-mediated tonic conductance that is driven by action potential-dependent GABA release. In contrast, unlabeled CeA neurons displayed a δ subunit-mediated tonic conductance that is enhanced by ethanol. Ethanol increased the firing discharge of CRF1 neurons and decreased the firing discharge of unlabeled CeA neurons. Retrograde tracing studies indicate that CeA CRF1 neurons project into the bed nucleus of the stria terminalis. Together, these data demonstrate subunit-specific tonic signaling and provide mechanistic insight into the specific effects of ethanol on CeA microcircuitry.
authors: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California 92037, USA. mherman@scripps.edu
authors: Melissa A
authors: MA
authors: Herman
authors: Candice
authors: C
authors: Contet
authors: Nicholas J
authors: NJ
authors: Justice
authors: Wylie
authors: W
authors: Vale
authors: Marisa
authors: M
authors: Roberto
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000679:Amygdala / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D021122:Protein Subunits / Q000502:physiology*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D000099052:CRF Receptor, Type 1
chemical_list: C546241:Gabra1 protein, mouse; D021122:Protein Subunits; D018019:Receptors, Corticotropin-Releasing Hormone; D011963:Receptors, GABA-A; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D000099052:CRF Receptor, Type 1