Contribution of the α5 GABAA receptor to the discriminative stimulus effects of propofol in rat

Propofol as an agonist of GABAA receptor has a rewarding and discriminative stimulus effect. However, which subtype of the GABAA receptor is involved in the discriminative stimulus effects of propofol is still not clear. We observed the effects of an agonist or an antagonist of the subtype-selective GABAA receptor on discriminative stimulus effects of propofol. Male Sprague-Dawley rats were trained to discriminate 10 mg/kg (intraperitoneal) propofol from intralipid under a fixed-ratio 10 schedule of food reinforcement. We found that propofol produced dose-dependent substitution for propofol at 10 mg/kg, with response rate reduction only at a dose above those producing the complete substitution. CL218,872 (1–3 mg/kg, intraperitoneal), an α1 subunit-selective GABAA receptor agonist, and SL651,498 (0.3–3 mg/kg, intraperitoneal), an α2/3 GABAA receptor selective agonist, could partially substitute for the discriminative stimulus effects of propofol (40–80% propofol-appropriate responding). Meanwhile, L838,417 (0.2–0.6 mg/kg, intravenous), a α2/3/5 GABAA receptor selective agonist, could produce near 100% propofol-appropriate responding and completely substitute for propofol effects. Moreover, the administration of L655,708, the α5 GABAA receptor inverse agonist, could dose dependently attenuate the discriminative stimulus of propofol. In contrast, the α1 GABAA receptor antagonist β-CCt (1–3 mg/kg) combined with propofol (10 mg/kg) failed to block the propofol effect. The data showed that propofol produces discriminative stimulus effects in a dose-dependent manner and acts mainly on the α5 GABAA to produce the discriminative stimulus effect. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://ift.tt/1hexVwJ *Benfu Wang and Kun Lv contributed equally to the writing of this article. Correspondence to Qing-Quan Lian, MD, Department of Anesthesiology, Second Affiliated Hospital and Institute of Neuroendocrinology, Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou 325000, People's Republic China Tel:+86 139 577 13889; e-mail: lianqingquanmz@163.com or Correspondence to Wen-hua Zhou, PhD, Laboratory of Behavioral Neuroscience, Ningbo Addiction, Research and Treatment Center, School of Medicine, Ningbo University, Zhejiang Province 42 Xibei St, Ningbo 315010, People's Republic China Tel:+86 138 058 47235; e-mail: whzhou@vip.163.com Received October 4, 2017 Accepted November 28, 2017 © 2018 Wolters Kluwer Health | Lippincott Williams & Wilkins

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2GhOU3U