Orexin type-2 receptor blockade prevents the nicotine-induced excitation of nucleus accumbens core neurons in rats: An electrophysiological perspective

Background: The nucleus accumbens core (NAcc) expresses both orexin and nicotinic acetylcholine receptors (nAChRs). Orexin is among important neurotransmitters, which regulates addictive properties of drugs of abuse including nicotine. The role of orexin-2 receptor (OX2R) in the regulation of NAcc neural activity in response to nicotine has not yet been studied. Hence, in this study, we examined whether the OX2R antagonist (TCS-OX2-29) can adjust the effects of nicotine on electrical activity of NAcc neurons, in urethane-anesthetized rats, using the single unit recording. Methods: Neuronal firing of NAcc was recorded for 15 min, then TCS-OX2-29 (OX2R-antagonist; 1, 3 and 10 ng/rat) or DMSO were microinjected into NAcc, just 5 min before subcutaneous (sc) administration of nicotine (0.5 mg/kg) or saline. The spontaneous firing activity was recorded for 70 min, after nicotine injection. Results: The results demonstrated that nicotine significantly excites the NAcc neurons and interestingly, the administration of TCS-OX2-29 (3 and 10 ng/rat) into the NAcc, inhibited nicotine-induced increases of NAcc neuronal responses. Furthermore, administration of TCS-OX2-29 (10 ng/rat), just 5 min before sc administration of saline instead of nicotine, did not significantly alter the neuronal responses, compared to the saline-control group. Conclusion: Our results showed that, although OX2R blockade alone did not affect neuronal activity in the NAcc, it was able to prevent the exciting effects of nicotine on NAcc neuronal activity. Therefore, we proposed that orexin has a potential modulator effect, in response to nicotine. (c) 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.