ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2021
Pituitary adenylate cyclase-activating polypeptide (PACAP) modulates dependence-induced alcohol drinking and anxiety-like behavior in male rats.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 35 citations in OpenAlex.
- Sustained hyperactivity of parasubthalamic nucleus by PACAP signaling mediates stress-induced anxiety.Molecular psychiatry · 2026Article
- A Distinct Subpopulation of Extended Amygdala Neurons Drives Food Intake.Biological psychiatry global open science · 2026Article
- The pituitary adenylate cyclase-activating polypeptide receptor and its splice variants: Unique roles in affective and motivated behavior.Journal of neuroendocrinology · 2026Review
- Alpha-2 Adrenergic Agonists Reduce Heavy Alcohol Drinking and Improve Cognitive Performance in Mice.eNeuro · 2026Article
- A Distinct Subpopulation of Extended Amygdala Neurons Drives Food Intake.bioRxiv : the preprint server for biology · 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 (PACAP)overexpression in the paraventricular nucleus of the thalamus alters motivated and affective behavior in female rats.Alcohol, clinical & experimental research · 2025Article
- Chronic alcohol withdrawal-associated increases in VTAAdvances in drug and alcohol research · 2025Article
- Pituitary adenylate cyclase-activating polypeptide plays a role in neuropsychiatric and substance use disorders: sex-specific perspective.Frontiers in neuroscience · 2025Review
- Impacts of chronic intermittent ethanol vapor and predator odor on ethanol intake and striatal DFrontiers in neuroscience · 2025Article
- Emerging pharmacological targets for alcohol use disorder.Alcohol (Fayetteville, N.Y.) · 2024Review
- Association between social dominance hierarchy and PACAP expression in the extended amygdala, corticosterone, and behavior in C57BL/6 male mice.Scientific reports · 2024Article
- Distinct eLPBTheranostics · 2024Article
- Article
- The functional heterogeneity of PACAP: Stress, learning, and pathology.Neurobiology of learning and memory · 2023Review
- Impact of social dominance hierarchy on PACAP expression in the extended amygdala, corticosterone, and behavior in C57BL/6 male mice.bioRxiv : the preprint server for biology · 2023Article
- Sex-related differences in endogenous pituitary adenylate cyclase-activating polypeptide (PACAP) in the thalamic paraventricular nucleus: Implications for addiction neuroscience.Addiction neuroscience · 2023Article
- Pituitary adenylate cyclase-activating polypeptide type 1 receptor within the nucleus accumbens core mediates excessive alcohol drinking in alcohol-preferring rats.Neuropharmacology · 2022Article
- Regulation of alcohol drinking by ventral striatum and extended amygdala circuitry.Neuropharmacology · 2022Review
- At the heart of the interoception network: Influence of the parasubthalamic nucleus on autonomic functions and motivated behaviors.Neuropharmacology · 2022Review
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5 authors at 1 institution in 1 country.
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Abstract
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.
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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.