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Corticotropin releasing factor-induced amygdala gamma-aminobutyric Acid release plays a key role in alcohol dependence.
Biol Psychiatry 2010; 67(9):831-9BP

Abstract

BACKGROUND

Corticotropin-releasing factor (CRF) and gamma-aminobutyric acid (GABA)ergic systems in the central amygdala (CeA) are implicated in the high-anxiety, high-drinking profile associated with ethanol dependence. Ethanol augments CeA GABA release in ethanol-naive rats and mice.

METHODS

Using naive and ethanol-dependent rats, we compared electrophysiologic effects and interactions of CRF and ethanol on CeA GABAergic transmission, and we measured GABA dialyzate in CeA after injection of CRF(1) antagonists and ethanol. We also compared mRNA expression in CeA for CRF and CRF(1) using real-time polymerase chain reaction. We assessed effects of chronic treatment with a CRF(1) antagonist on withdrawal-induced increases in alcohol consumption in dependent rats.

RESULTS

CRF and ethanol augmented CeA GABAergic transmission in naive rats via increased GABA release. Three CRF1 receptor (CRF(1)) antagonists decreased basal GABAergic responses and abolished ethanol effects. Ethanol-dependent rats exhibited heightened sensitivity to CRF and CRF(1) antagonists on CeA GABA release. Intra-CeA CRF(1) antagonist administration reversed dependence-related elevations in GABA dialysate and blocked ethanol-induced increases in GABA dialyzate in both dependent and naive rats. Polymerase chain reaction studies indicate increased expression of CRF and CRF(1) in CeA of dependent rats. Chronic CRF(1) antagonist treatment blocked withdrawal-induced increases in alcohol drinking by dependent rats and tempered moderate increases in alcohol consumption by nondependent rats in intermittent testing.

CONCLUSIONS

These combined findings suggest a key role for specific presynaptic CRF-GABA interactions in CeA in the development and maintenance of ethanol dependence.

Authors+Show Affiliations

Committee on the Neurobiology of Addictive Disorders, Scripps Research Institute, La Jolla, California 92037, USA. mroberto@scripps.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20060104

Citation

Roberto, Marisa, et al. "Corticotropin Releasing Factor-induced Amygdala Gamma-aminobutyric Acid Release Plays a Key Role in Alcohol Dependence." Biological Psychiatry, vol. 67, no. 9, 2010, pp. 831-9.
Roberto M, Cruz MT, Gilpin NW, et al. Corticotropin releasing factor-induced amygdala gamma-aminobutyric Acid release plays a key role in alcohol dependence. Biol Psychiatry. 2010;67(9):831-9.
Roberto, M., Cruz, M. T., Gilpin, N. W., Sabino, V., Schweitzer, P., Bajo, M., ... Parsons, L. H. (2010). Corticotropin releasing factor-induced amygdala gamma-aminobutyric Acid release plays a key role in alcohol dependence. Biological Psychiatry, 67(9), pp. 831-9. doi:10.1016/j.biopsych.2009.11.007.
Roberto M, et al. Corticotropin Releasing Factor-induced Amygdala Gamma-aminobutyric Acid Release Plays a Key Role in Alcohol Dependence. Biol Psychiatry. 2010 May 1;67(9):831-9. PubMed PMID: 20060104.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Corticotropin releasing factor-induced amygdala gamma-aminobutyric Acid release plays a key role in alcohol dependence. AU - Roberto,Marisa, AU - Cruz,Maureen T, AU - Gilpin,Nicholas W, AU - Sabino,Valentina, AU - Schweitzer,Paul, AU - Bajo,Michal, AU - Cottone,Pietro, AU - Madamba,Samuel G, AU - Stouffer,David G, AU - Zorrilla,Eric P, AU - Koob,George F, AU - Siggins,George R, AU - Parsons,Loren H, Y1 - 2010/01/08/ PY - 2009/09/16/received PY - 2009/11/10/revised PY - 2009/11/11/accepted PY - 2010/1/12/entrez PY - 2010/1/12/pubmed PY - 2010/6/29/medline SP - 831 EP - 9 JF - Biological psychiatry JO - Biol. Psychiatry VL - 67 IS - 9 N2 - BACKGROUND: Corticotropin-releasing factor (CRF) and gamma-aminobutyric acid (GABA)ergic systems in the central amygdala (CeA) are implicated in the high-anxiety, high-drinking profile associated with ethanol dependence. Ethanol augments CeA GABA release in ethanol-naive rats and mice. METHODS: Using naive and ethanol-dependent rats, we compared electrophysiologic effects and interactions of CRF and ethanol on CeA GABAergic transmission, and we measured GABA dialyzate in CeA after injection of CRF(1) antagonists and ethanol. We also compared mRNA expression in CeA for CRF and CRF(1) using real-time polymerase chain reaction. We assessed effects of chronic treatment with a CRF(1) antagonist on withdrawal-induced increases in alcohol consumption in dependent rats. RESULTS: CRF and ethanol augmented CeA GABAergic transmission in naive rats via increased GABA release. Three CRF1 receptor (CRF(1)) antagonists decreased basal GABAergic responses and abolished ethanol effects. Ethanol-dependent rats exhibited heightened sensitivity to CRF and CRF(1) antagonists on CeA GABA release. Intra-CeA CRF(1) antagonist administration reversed dependence-related elevations in GABA dialysate and blocked ethanol-induced increases in GABA dialyzate in both dependent and naive rats. Polymerase chain reaction studies indicate increased expression of CRF and CRF(1) in CeA of dependent rats. Chronic CRF(1) antagonist treatment blocked withdrawal-induced increases in alcohol drinking by dependent rats and tempered moderate increases in alcohol consumption by nondependent rats in intermittent testing. CONCLUSIONS: These combined findings suggest a key role for specific presynaptic CRF-GABA interactions in CeA in the development and maintenance of ethanol dependence. SN - 1873-2402 UR - https://www.unboundmedicine.com/medline/citation/20060104/Corticotropin_releasing_factor_induced_amygdala_gamma_aminobutyric_Acid_release_plays_a_key_role_in_alcohol_dependence_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-3223(09)01328-6 DB - PRIME DP - Unbound Medicine ER -