Abstract
Background: The receptor for nociceptin/orphanin‐FQ (NOP) is localized in the mesolimbic reward pathway and has been suggested to play a role in addiction and motivated behavior. We characterize here a novel, potent, orally‐bioavailable NOP antagonist in several ethanol self‐administration models.Methods: Compound 1 was evaluated in homecage ethanol self‐administration models, progressive ratio operant self‐administration, stress‐induced reinstatement to ethanol‐seeking, and in vivo microdialysis.Results: Compound 1 dose‐dependently reduced homecage ethanol self‐administration in both P and msP rats, without affecting food or water intake. Compound 1 also attenuated progressive ratio operant responding and breakpoints in P rats. Stress‐induced reinstatement of ethanol‐seeking in msP rats was completely blocked by compound 1. Furthermore, compound 1 blocked ethanol‐induced dopamine release in the nucleus accumbens.Conclusions: Compound 1 demonstrates efficacy in attenuating ethanol self‐administration and stress‐induced ethanol‐seeking in two different lines of rats that exhibit excessive ethanol consumption. Compound 1 also blocks the motivation to consume ethanol and ethanol‐stimulated increases in extracellular dopamine levels in the nucleus accumbens, suggesting potential therapeutic utility of NOP receptor antagonists in treating alcohol addiction.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have