Pituitary adenylate cyclase-activating polypeptide type 1 receptor within the nucleus accumbens core mediates excessive alcohol drinking in alcohol-preferring rats.

Alcohol Drinking / drug therapy Alcoholism / drug therapy Animals Nucleus Accumbens / metabolism Pituitary Adenylate Cyclase-Activating Polypeptide / pharmacology Rats Rats, Wistar Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / antagonists & inhibitors

Journal

Neuropharmacology
ISSN: 1873-7064
Titre abrégé: Neuropharmacology
Pays: England
ID NLM: 0236217

Informations de publication

Date de publication:
01 07 2022
Historique:
received: 04 02 2022
revised: 19 03 2022
accepted: 12 04 2022
pubmed: 24 4 2022
medline: 20 5 2022
entrez: 23 4 2022
Statut: ppublish

Résumé

Alcohol use disorders (AUD) have a strong component of heritability; however, the neurobiological mechanisms mediating the propensity to consume excessive amounts of alcohol are still not well understood. Pituitary adenylate cyclase-activating polypeptide (PACAP), a highly conserved neuropeptide which exerts its effects mainly through the PAC1 receptor (PAC1R), has been suggested to be one of the mediators of the effects of drugs of abuse and alcohol. Here, we investigated the role of the PACAP/PAC1R system in excessive alcohol drinking in alcohol-preferring rats, an established animal model of AUD. Intracerebroventricular (i.c.v.) administration of the PAC1R antagonist PACAP(6-38) blocked excessive alcohol drinking and motivation to drink in Sardinian alcohol-preferring (Scr:sP) rats, without affecting water, saccharin, or sucrose intake. Notably, PACAP(6-38) did not affect ethanol responding in outbred Wistar rats. PACAP(6-38) also significantly reduced alcohol-seeking behavior under a second-order schedule of reinforcement. Using immunohistochemistry, a significant increase in the number of PAC1R positive cells was observed selectively in the nucleus accumbens (NAcc) Core of Scr:sP rats, compared to Wistar rats, following alcohol drinking. Finally, excessive drinking in Scr:sP rats was suppressed by intra-NAcc Core, but not intra-NAcc Shell, PACAP(6-38), as well as by virally-mediated PAC1R knockdown in the NAcc Core. The present study shows that hyperactivity of the PACAP/PAC1R system specifically in the NAcc Core mediates excessive drinking of alcohol-preferring rats, and indicates that this system may represent a novel target for the treatment of AUD.

Identifiants

DOI: 10.1016/j.neuropharm.2022.109063 PMID: 35460713 PMC: PMC10342914
pubmed: 35460713
pii: S0028-3908(22)00122-8
doi: 10.1016/j.neuropharm.2022.109063
pmc: PMC10342914
mid: NIHMS1911292
pii:
doi:

Substances chimiques

Pituitary Adenylate Cyclase-Activating Polypeptide 0
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

109063

Subventions

Organisme : NIAAA NIH HHS
ID : R21 AA026051
Pays : United States
Organisme : NIAAA NIH HHS
ID : R21 AA029495
Pays : United States
Organisme : NIAAA NIH HHS
ID : R00 AA016731
Pays : United States
Organisme : NIAAA NIH HHS
ID : F30 AA028184
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA025038
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA024439
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH113128
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH093650
Pays : United States

Informations de copyright

Copyright © 2022 Elsevier Ltd. All rights reserved.

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Auteurs

Margaret A Minnig (MA)

Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA.

Angelo Blasio (A)

Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA.

Antonio Ferragud (A)

Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA.

Yasmine N Sami (YN)

Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA.

Emily E Erhard (EE)

Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA.

Rose H Clark (RH)

Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA.

Alyssa DiLeo (A)

Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA.

Chiara Giuliano (C)

Behavioral and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK.

Barry J Everitt (BJ)

Behavioral and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Cambridge, UK.

Pietro Cottone (P)

Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA.

Valentina Sabino (V)

Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA. Electronic address: vsabino@bu.edu.

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Classifications MeSH

questionsmedicales.fr › Comportement et mécanismes comportementaux › Comportement › Comportement dipsique › Consommation d'alcool › Pituitary adenylate cyclase-activating...
questionsmedicales.fr › Troubles mentaux › Troubles liés à une substance › Troubles liés à l'alcool › Alcoolisme › Pituitary adenylate cyclase-activating...
questionsmedicales.fr › Eucaryotes › Animaux › Pituitary adenylate cyclase-activating...
questionsmedicales.fr › Système nerveux › Système nerveux central › Encéphale › Prosencéphale › Télencéphale › Cerveau › Noyaux gris centraux › Corps strié › Striatum ventral › Noyau accumbens › Pituitary adenylate cyclase-activating...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Facteurs de croissance nerveuse › Polypeptide activateur de l'adénylcyclase hypophysaire › Pituitary adenylate cyclase-activating...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Pituitary adenylate cyclase-activating...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Rat Wistar › Pituitary adenylate cyclase-activating...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs couplés aux protéines G › Récepteurs au polypeptide activateur de l'adénylcyclase hypophysaire › Récepteur de type I au polypeptide activateur de l'adénylcyclase hypophysaire › Pituitary adenylate cyclase-activating...