Carter Lawrence P, Chen Weibin, Coop Andrew, Koek Wouter, France Charles P
Department of Pharmacology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229, USA.
Eur J Pharmacol. 2006 May 24;538(1-3):85-93. doi: 10.1016/j.ejphar.2006.03.039. Epub 2006 Mar 24.
The aim of this study was to examine the possible heterogeneity of mechanisms that contribute to the discriminative stimulus and rate-decreasing effects of gamma-hydroxybutyrate (GHB). Dose effect curves were determined for GHB and two GABA(B) receptor agonists (baclofen and SKF97541) alone and together with the selective GABA(B) receptor antagonist CGP35348 in rats discriminating GHB. In a second study, GHB and SKF97541 dose effect curves were determined alone and together with baclofen. CGP35348 attenuated the discriminative stimulus and rate-decreasing effects of SKF97541 and baclofen to a greater extent than those of GHB. In the second study, baclofen enhanced the discriminative stimulus and rate-decreasing effects of GHB and SKF97541; however, the GHB dose effect curve was not shifted in a parallel manner. Taken together, these data suggest that multiple mechanisms, possibly including GHB receptors and GABA(B) receptor subtypes, are involved in the discriminative stimulus and rate-decreasing effects of GHB.
本研究的目的是检验导致γ-羟基丁酸（GHB）辨别性刺激和速率降低效应的机制可能存在的异质性。在辨别GHB的大鼠中，分别测定了GHB和两种GABA(B)受体激动剂（巴氯芬和SKF97541）单独使用时以及与选择性GABA(B)受体拮抗剂CGP35348共同使用时的剂量效应曲线。在第二项研究中，分别测定了GHB和SKF97541单独使用时以及与巴氯芬共同使用时的剂量效应曲线。CGP35348对SKF97541和巴氯芬辨别性刺激和速率降低效应的减弱程度大于对GHB的减弱程度。在第二项研究中，巴氯芬增强了GHB和SKF97541的辨别性刺激和速率降低效应；然而，GHB的剂量效应曲线并未平行移动。综上所述，这些数据表明，多种机制，可能包括GHB受体和GABA(B)受体亚型，参与了GHB的辨别性刺激和速率降低效应。
