Effects of pharmacological and environmental manipulations on choice between fentanyl and shock avoidance/escape in male and female rats under mutually exclusive and non-exclusive choice conditions.

Autor: Marcus MM; Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA., Marsh SA; Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA., Arriaga M; Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA., Negus SS; Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA., Banks ML; Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA. mbanks7@vcu.edu.
Jazyk: angličtina
Zdroj: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2024 Dec; Vol. 49 (13), pp. 2011-2021. Date of Electronic Publication: 2024 Aug 05.
DOI: 10.1038/s41386-024-01939-7
Abstrakt: Substance use disorders are defined by persistent drug consumption despite adverse consequences. Accordingly, we developed two fentanyl-vs-shock avoidance/escape choice procedures in which male and female rats responded under a fixed-ratio (FR)1:FR1 concurrent schedule of shock avoidance/escape and IV fentanyl under either mutually exclusive or non-exclusive choice conditions. Initial experiments using a discrete-trial procedure determined behavioral allocation between mutually exclusive shock avoidance/escape and different fentanyl doses (0.32-18 μg/kg/infusion; Experiment 1). Shock intensity (0.1-0.7 mA) and shock avoidance/escape response requirement (FR1-16) were also manipulated (Experiment 2). Next, we used a free-operant procedure in which shock avoidance/escape and fentanyl were continuously available under non-exclusive conditions, and response-shock (R-S) interval (30-1000 s) was manipulated (Experiment 3). Finally, we tested the hypothesis that extended-access fentanyl self-administration would produce fentanyl dependence, establish fentanyl withdrawal as an endogenous negative reinforcer, and increase fentanyl choice in both procedures (Experiments 4 and 5). The shock avoidance/escape contingency decreased fentanyl self-administration, and rats consistently chose shock avoidance/escape over fentanyl in both choice conditions. Decreasing shock intensity or increasing shock avoidance/escape response requirement failed to increase fentanyl choice, suggesting that fentanyl and shock avoidance/escape are independent economic commodities. Increasing the R-S interval increased fentanyl choice but failed to increase shock delivery. Extended fentanyl access engendered high fentanyl intake and opioid withdrawal signs but failed to increase fentanyl choice under either choice condition. These results suggest that neither positive fentanyl reinforcement nor negative reinforcement by fentanyl withdrawal is sufficient to reduce shock avoidance/escape-maintained responding and increase foot shock as an adverse consequence.
(© 2024. The Author(s).)
Databáze: MEDLINE
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