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Investigating how environmental factors, such as the availability of non-ethanol alternative reinforcers, influences ethanol self-administration is critical for understanding the pathology of alcohol use disorder (AUD). Here we established the first operant choice paradigm that leverages the strengths of the sipper tube self-administration model to investigate how concurrent access to sucrose altered ethanol self-administration in male and female Long Evans rats. Choice behavior was examined using two distinct paradigms, including a novel adaptation of the response requirement paradigm. Under both a fixed-ratio or response requirement paradigm, we observed that concurrent availability of an alternative reinforcer significantly reduced appetitive and consummatory ethanol drinking-related behaviors. Furthermore, we assessed the sensitivity of the response requirement choice paradigm by administering the pharmacological stressor yohimbine and by altering the taste of the ethanol solution. Yohimbine administration non-selectively increased ethanol and sucrose intake, but not seeking, while taste adulteration decreased ethanol seeking and intake. These experiments demonstrate the utility of two concurrent choice paradigms that can more accurately capture AUD-like phenotypes, such as ethanol-directed choice in the face of alternative reinforcers. Future studies should investigate how models of vulnerability and dependence alter ethanol choice behavior under these paradigms.
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http://dx.doi.org/10.1016/j.addicn.2025.100196 | DOI Listing |
J Exp Anal Behav
September 2025
Faillace Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, USA.
Polydrug abuse is the persistent self-administration of more than one reinforcing drug. The present study provided rhesus monkeys concurrent access to two drugs: 8% alcohol and solutions of either cocaine or methadone. The liquids were available under concurrent nonindependent fixed-ratio (FR) schedules across increasing and then decreasing ratio sizes.
View Article and Find Full Text PDFNeuropsychopharmacology
September 2025
Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Excessive alcohol use causes a great deal of harm and negative health outcomes. Corticotrophin releasing factor (CRF), a stress-related neuropeptide, has been implicated in binge ethanol intake and ethanol dependence in rodents. CRF containing neurons in the bed nucleus of the stria terminalis (BNST) can influence ethanol consumption.
View Article and Find Full Text PDFMethods Mol Biol
August 2025
School of Chemistry, Indian Institute of Science Education and Research Thiruvananthapuram, Maruthamala PO, Vithura, Kerala, India.
The development of lipid-based nanoparticles (LNPs) has significantly advanced the field of drug delivery, particularly for nucleic acids, such as mRNA being clinically used in the vaccines against COVID-19. This chapter explores the structural composition and functional properties of LNPs, including key components, such as ionizable cationic lipids, neutral/helper phospholipids, cholesterol, and lipid-anchored polyethylene glycol (PEG) constructs. The discussion includes the role of these components in improving the stability, biocompatibility, and delivery efficiency of LNPs.
View Article and Find Full Text PDFNeuropharmacology
November 2025
Department of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, TX, 77807, United States. Electronic address:
Relapse remains a major challenge in the treatment of alcohol use disorder, driven in part by persistent neuroadaptations. However, how different post-alcohol experiences, such as passive withdrawal (abstinence) versus active extinction training, differentially shape the neural circuits and synaptic mechanisms that influence relapse vulnerability remains unclear. Here, we show that these experiences have opposing effects on dorsomedial striatal (DMS) direct-pathway medium spiny neurons (dMSNs) and dopamine dynamics during cue-induced reinstatement of alcohol seeking.
View Article and Find Full Text PDFNeuropharmacology
November 2025
School of Psychology, University of New South Wales, UNSW, Sydney, 2052, Australia. Electronic address:
Alcohol Use Disorder (AUD) is a chronic relapsing disorder affecting more than 400 million people globally. Glucagon-like peptide-1 (GLP-1) has recently shown promise as a treatment for AUD but the underlying neural mechanisms are unclear. Given that dorsolateral septum (dLS) highly expresses GLP-1 receptors and is implicated in reward processing, this study investigated whether GLP-1 reduces ethanol intake and relapse behaviors via dLS.
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