ArticleNeuropharmacology2022
Pituitary adenylate cyclase-activating polypeptide type 1 receptor within the nucleus accumbens core mediates excessive alcohol drinking in alcohol-preferring rats.
Article in Neuropharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 10 citations in OpenAlex.
- The pituitary adenylate cyclase-activating polypeptide receptor and its splice variants: Unique roles in affective and motivated behavior.Journal of neuroendocrinology · 2026Review
- PACAP Signalling Network in the Nucleus Accumbens Core Regulates Reinstatement Behaviour in Rat.Addiction biology · 2025Article
- Pituitary adenylate cyclase-activating polypeptide (PACAP)overexpression in the paraventricular nucleus of the thalamus alters motivated and affective behavior in female rats.Alcohol, clinical & experimental research · 2025Article
- Repeated cycles of binge-like ethanol consumption and abstinence alter neuropeptide mRNA in prefrontal and insular cortex, amygdala, and lateral hypothalamus of male and female C57BL/6J mice.Alcohol, clinical & experimental research · 2025Article
- Pituitary adenylate cyclase-activating polypeptide plays a role in neuropsychiatric and substance use disorders: sex-specific perspective.Frontiers in neuroscience · 2025Review
- Emerging pharmacological targets for alcohol use disorder.Alcohol (Fayetteville, N.Y.) · 2024Review
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.