title: Glutamatergic transmission in the central nucleus of the amygdala is selectively altered in Marchigian Sardinian alcohol-preferring rats: Alcohol and CRF effects.
abstract: The CRF system of the central nucleus of the amygdala (CeA) is important for the processing of anxiety, stress, and effects of acute and chronic ethanol. We previously reported that ethanol decreases evoked glutamate transmission in the CeA of Sprague Dawley rats and that ethanol dependence alters glutamate release in the CeA. Here, we examined the effects of ethanol, CRF and a CRF1 receptor antagonist on spontaneous and evoked glutamatergic transmission in CeA neurons from Wistar and Marchigian Sardinian Preferring (msP) rats, a rodent line genetically selected for excessive alcohol drinking and characterized by heightened activity of the CRF1 system. Basal spontaneous and evoked glutamate transmission in CeA neurons from msP rats was increased compared to Wistar rats. Ethanol had divergent effects, either increasing or decreasing spontaneous glutamate release in the CeA of Wistar rats. This bidirectional effect was retained in msP rats, but the magnitude of the ethanol-induced increase in glutamate release was significantly smaller. The inhibitory effect of ethanol on evoked glutamatergic transmission was similar in both strains. CRF also either increased or decreased spontaneous glutamate release in CeA neurons of Wistar rats, however, in msP rats CRF only increased glutamate release. The inhibitory effect of CRF on evoked glutamatergic transmission was also lost in neurons from msP rats. A CRF1 antagonist produced only minor effects on spontaneous glutamate transmission, which were consistent across strains, and no effects on evoked glutamate transmission. These results demonstrate that the genetically altered CRF system of msP rats results in alterations in spontaneous and stimulated glutamate signaling in the CeA that may contribute to both the anxiety and drinking behavioral phenotypes.
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Herman
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Florence P
authors.initials: FP
authors.lastname: Varodayan
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Oleata
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: George
authors.initials: G
authors.lastname: Luu
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Dean
authors.initials: D
authors.lastname: Kirson
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Laboratory of Clinical and Translational Sciences, National Institutes of Health, Bldg.10-CRC/Rm. 1-5330, 10 Center Drive, Bethesda, MD 20892-1108, USA.
authors.forename: Markus
authors.initials: M
authors.lastname: Heilig
authors.affiliation: School of Pharmacy, Pharmacology Unit, University of Camerino, Via Madonna delle Carceri, 62032 Camerino, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ciccocioppo
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA. Electronic address: mroberto@scripps.edu.
authors.forename: Marisa
authors.initials: M
authors.lastname: Roberto
mesh_terms: D000428:Alcohol Drinking / Q000378:metabolism*; D000818:Animals; D066274:Central Amygdaloid Nucleus / Q000187:drug effects / Q000378:metabolism*; D000431:Ethanol / Q000008:administration & dosage*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*
chemical_list: D011743:Pyrimidines; C412383:R 121919; D018019:Receptors, Corticotropin-Releasing Hormone; D000431:Ethanol; D018698:Glutamic Acid
keywords: Alcohol; Amygdala; CRF; CRF1 antagonist; Electrophysiology; Glutamate