Antagonism of μ-opioid receptors reduces sensation seeking-like behavior in mice

• Published in: Behavioural brain research 2019-02, Vol.359, p.498-501
• Main Authors: Sikora, Magdalena, Skupio, Urszula, Jastrzebska, Kamila, Rodriguez Parkitna, Jan, Przewlocki, Ryszard
• Format: Article
• Language: English
• Subjects: Animals; Appetitive Behavior - drug effects; Appetitive Behavior - physiology; Brain - drug effects; Brain - metabolism; Conditioned place aversion; Conditioning, Operant - drug effects; Conditioning, Operant - physiology; Dose-Response Relationship, Drug; Exploratory Behavior - drug effects; Exploratory Behavior - physiology; Male; Mice, Inbred C57BL; Morphinans - pharmacology; Motivation - drug effects; Motivation - physiology; Motor Activity - drug effects; Motor Activity - physiology; Naltrexone - analogs & derivatives; Naltrexone - pharmacology; Narcotic Antagonists - pharmacology; Opioids; Random Allocation; Receptors, Opioid - metabolism; Receptors, Opioid, mu - metabolism; Reward; Sensation seeking; μ-Opioid receptor
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2018.11.039

•Operant novelty-seeking behavior recruits the endogenous opioid system.•Selective μ opioid antagonist (but not δ or κ) attenuates reward-seeking.•Cyprodime does not induce conditioned place aversion. Novelty- and sensation-seeking behaviors induce activity of the brain reward system and are associated with increased susceptibility to drug abuse. Endogenous opioids have been implicated in reward-related behavior; however, the involvement of specific opioid receptors in the mechanism of sensation seeking is unknown. Here, we show that selective inhibition of opioid receptors reduce operant sensation seeking in mice. Administration of naltrexone (a nonselective opioid antagonist) reduced instrumental responding for sensory stimuli at one of the tested doses (2 mg/kg). More robust effects were observed in the case of cyprodime, a selective μ opioid receptor antagonist, which reduced instrumental responses by ∼50% at doses of 0.5 mg/kg and larger. Conversely, selective δ and κ receptor antagonists (naltrindole and nor-binaltorphimine, respectively) had no effect on sensation-seeking behavior. Importantly, while naltrexone produces aversion in the conditioned place preference test, cyprodime had no such effect. Therefore, reduced instrumental responding was not correlated with aversive effects of the opioid antagonists. In conclusion, our results revealed a novel mechanism of action of selective opioid receptors antagonists, which may have relevance for their efficacy in the treatment of drug abuse.