Colombo G, Agabio R, Lobina C, Reali R, Gessa G L
C.N.R. Center for Neuropharmacology, Cagliari, Italy.
Physiol Behav. 1998 Jun 1;64(3):293-302. doi: 10.1016/s0031-9384(98)00062-6.
The present study was designed to further investigate the pharmacological profile of the discriminative stimulus effects of gamma-hydroxybutyric acid (GHB). Drugs acting at the gamma-aminobutyric acid (GABA)B receptor (baclofen and CGP 35348), GABA(A)/benzodiazepine receptor complex (diazepam), N-methyl-D-aspartate (NMDA) receptor complex (dizocilpine), and cannabinoid receptor (WIN 55,212-2) were tested for substitution or blockade of the GHB interoceptive cue in rats trained to discriminate either 300 or 700 mg/kg of GHB i.g. from water in a T-maze, food-reinforced drug discrimination paradigm. Baclofen completely substituted for both training doses of GHB; however, its potency in substituting for GHB increased as the training dose of GHB was increased. CGP 35348 partially and completely blocked the cue elicited by 300 and 700 mg/kg of GHB, respectively. In contrast, diazepam partially substituted for 300 mg/kg of GHB, while failing to produce a GHB-appropriate response in the rat group trained to the higher GHB dose. Neither dizocilpine nor WIN 55,212-2 substituted for GHB. Collectively, these data suggest that: a) GHB produces a compound stimulus; and b) GABA(B)- and GABA(A)-mediated cues are prominent components of the mixed stimulus of GHB. However, the quality (i.e., the proportion of the component cues) of the stimulus varies as the training dose of GHB is increased; indeed, the contribution of the GABA(A)- and GABA(B)-mediated cues were smaller and greater, respectively, at 700 and 300 mg/kg of GHB training doses.
本研究旨在进一步探究γ-羟基丁酸（GHB）辨别刺激效应的药理学特征。在以食物强化的药物辨别范式的T迷宫中，对作用于γ-氨基丁酸（GABA）B受体的药物（巴氯芬和CGP 35348）、GABA(A)/苯二氮䓬受体复合物（地西泮）、N-甲基-D-天冬氨酸（NMDA）受体复合物（地佐环平）和大麻素受体（WIN 55,212-2）进行测试，以观察其对训练辨别腹腔注射300或700 mg/kg GHB与水的大鼠体内GHB内感受性线索的替代或阻断作用。巴氯芬完全替代了两种训练剂量的GHB；然而，其替代GHB的效力随着GHB训练剂量的增加而增强。CGP 35348分别部分和完全阻断了300和700 mg/kg GHB引发的线索。相比之下，地西泮部分替代了300 mg/kg的GHB，但在训练至较高GHB剂量的大鼠组中未能产生与GHB相符的反应。地佐环平和WIN 55,212-2均未替代GHB。总体而言，这些数据表明：a）GHB产生复合刺激；b）GABA(B)和GABA(A)介导的线索是GHB混合刺激的主要成分。然而，随着GHB训练剂量的增加，刺激的性质（即成分线索的比例）会发生变化；实际上，在300和700 mg/kg GHB训练剂量下，GABA(A)和GABA(B)介导的线索贡献分别较小和较大。
