Inhibitory and excitatory alcohol-seeking cues distinct roles in behavior, neurochemistry, and mesolimbic pathway in alcohol preferring (P) rats.

Autor: Hauser SR; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: shhauser@iupui.edu., Deehan GA Jr; Department of Psychology, East Tennessee State University, Johnson City, TN 37614, USA., Knight CP; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Waeiss RA; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Engleman EA; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Ding ZM; Department of Anesthesiology and Perioperative Medicine, Department of Pharmacology, The Pennsylvania State University, Penn State College of Medicine, Hershey, PA 17033, USA., Johnson PL; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA., McBride WJ; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Truitt WA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Anatomy, Cell Biology & Physiology, Indiana University School of Medicine, Indianapolis, IN 46202, USA., Rodd ZA; Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Jazyk: angličtina
Zdroj: Drug and alcohol dependence [Drug Alcohol Depend] 2023 May 01; Vol. 246, pp. 109858. Date of Electronic Publication: 2023 Mar 29.
DOI: 10.1016/j.drugalcdep.2023.109858
Abstrakt: Cues associated with alcohol use can readily enhance self-reported cravings for alcohol, which increases the likelihood of reusing alcohol. Understanding the neuronal mechanisms involved in alcohol-seeking behavior is important for developing strategies to treat alcohol use disorder. In all experiments, adult female alcohol-preferring (P) rats were exposed to three conditioned odor cues; CS+ associated with EtOH self-administration, CS- associated with the absence of EtOH (extinction training), and a CS 0, a neutral stimulus. The data indicated that presentation of an excitatory conditioned cue (CS+) can enhance EtOH- seeking while the CS- can inhibit EtOH-seeking under multiple test conditions. Presentation of the CS+ activates a subpopulation of dopamine neurons within the interfascicular nucleus of the posterior ventral tegmental area (posterior VTA) and basolateral amygdala (BLA). Pharmacological inactivation of the BLA with GABA agonists inhibits the ability of the CS+ to enhance EtOH-seeking but does not alter context-induced EtOH-seeking or the ability of the CS- to inhibit EtOH-seeking. Presentation of the conditioned odor cues in a non-drug-paired environment indicated that presentation of the CS+ increased dopamine levels in the BLA. In contrast, presentation of the CS- decreased both glutamate and dopamine levels in the BLA. Further analysis revealed that presentation of a CS+ EtOH-associated conditioned cue activates GABA interneurons but not glutamate projection neurons. Overall, the data indicate that excitatory and inhibitory conditioned cues can contrarily alter EtOH-seeking behaviors and that different neurocircuitries are mediating these distinct cues in critical brain regions. Pharmacotherapeutics for craving should inhibit the CS+ and enhance the CS- neurocircuits.
Competing Interests: Conflict of interest None of the authors has a conflict of interest associated with this research.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: