Pituitary adenylate cyclase-activating polypeptide (PACAP) modulates dependence-induced alcohol drinking and anxiety-like behavior in male rats.

Tytuł:: Pituitary adenylate cyclase-activating polypeptide (PACAP) modulates dependence-induced alcohol drinking and anxiety-like behavior in male rats.
Autorzy:: Ferragud A; Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA.
Velazquez-Sanchez C; Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA.
Minnig MA; Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA.
Sabino V; Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA. .
Cottone P; Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA. .
Źródło:: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2021 Feb; Vol. 46 (3), pp. 509-518. Date of Electronic Publication: 2020 Nov 16.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: 2003- : London : Nature Publishing Group
Original Publication: [New York, NY] : Elsevier, [c1987-
MeSH Terms:: Septal Nuclei*/metabolism
Pituitary Adenylate Cyclase-Activating Polypeptide/*metabolism
Alcohol Drinking ; Animals ; Anxiety/drug therapy ; Emotions ; Male ; Rats ; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
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Grant Information:: R21 AA026051 United States AA NIAAA NIH HHS; R01 AA025038 United States AA NIAAA NIH HHS; R01 AA024439 United States AA NIAAA NIH HHS; R21 MH113128 United States MH NIMH NIH HHS; R01 MH093650 United States MH NIMH NIH HHS
Substance Nomenclature:: 0 (Pituitary Adenylate Cyclase-Activating Polypeptide)
0 (Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I)
Entry Date(s):: Date Created: 20201116 Date Completed: 20210623 Latest Revision: 20220531
Update Code:: 20240105
PubMed Central ID:: PMC8027820
DOI:: 10.1038/s41386-020-00904-4
PMID:: 33191400
: Czasopismo naukowe

Alcohol use disorder (AUD) is a devastating illness defined by periods of heavy drinking and withdrawal, often leading to a chronic relapsing course. Initially, alcohol is consumed for its positive reinforcing effects, but later stages of AUD are characterized by drinking to alleviate withdrawal-induced negative emotional states. Brain stress response systems in the extended amygdala are recruited by excessive alcohol intake, sensitized by repeated withdrawal, and contribute to the development of addiction. In this study, we investigated one such brain stress response system, pituitary adenylate cyclase-activating polypeptide (PACAP), and its cognate receptor, PAC1R, in alcohol withdrawal-induced behaviors. During acute withdrawal, rats exposed to chronic intermittent ethanol vapor (ethanol-dependent) displayed a significant increase in PACAP levels in the bed nucleus of the stria terminalis (BNST), a brain area within the extended amygdala critically involved in both stress and withdrawal. No changes in PACAP levels were observed in the central nucleus of the amygdala. Site-specific microinfusion of the PAC1R antagonist PACAP(6-38) into the BNST dose-dependently blocked excessive alcohol intake in ethanol-dependent rats without affecting water intake overall or basal ethanol intake in control, nondependent rats. Intra-BNST PACAP(6-38) also reversed ethanol withdrawal-induced anxiety-like behavior in ethanol-dependent rats, but did not affect this measure in control rats. Our findings show that chronic intermittent exposure to ethanol recruits the PACAP/PAC1R system of the BNST and that these neuroadaptations mediate the heightened alcohol drinking and anxiety-like behavior observed during withdrawal, suggesting that this system represents a major brain stress element responsible for the negative reinforcement associated with the "dark side" of alcohol addiction.

Comment in: Neuropsychopharmacology. 2021 Feb;46(3):489-490. (PMID: 33257754)

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