Commissaris R L, Vasas R J, McCloskey T C
Department of Pharmaceutical Sciences, College of Pharmacy & AHP, Wayne State University, Detroit, MI 48202.
Pharmacol Biochem Behav. 1988 Mar;29(3):631-4. doi: 10.1016/0091-3057(88)90031-7.
Typical barbiturates produce a spectrum of behavioral effects, including anti-convulsant, muscle relaxant, sedative hypnotic and anti-anxiety actions. In contrast to these typical barbiturates, there exists a group of barbiturates which are pro-, rather than anti-convulsant. The effects of these convulsant barbiturates on anxiety-related behaviors have not been examined. Therefore, the present studies were designed to compare the effects of the convulsant barbiturate CHEB to those of a number of typical barbiturates in the Conditioned Suppression of Drinking (CSD) paradigm, an "animal model" for the study of anxiety and anti-anxiety agents. In daily 10-minute sessions, water-deprived rats were trained to drink from a tube which was occasionally electrified (0.5 mA), electrification being signalled by a tone. Within 3-4 weeks control responding had stabilized (10-15 shocks and 10-15 ml water/session); drug tests were then conducted at weekly intervals. Consistent with previous reports, typical barbiturates (pentobarbital, secobarbital, phenobarbital) produced dose-dependent increases in the number of shocks received at doses which did not depress background responding (water intake). In contrast, sub-convulsant doses of CHEB (0.3-2.5 mg/kg) produced a dose-dependent depression of both punished responding and background responding. Finally, it was found that pre-treatment with 1.25 mg/kg CHEB did not alter the anti-conflict effects of pentobarbital. These results suggest that (1) convulsant and typical barbiturates have markedly different effects on conflict behavior in the rat and (2) CHEB appears not to possess any "barbiturate antagonist" qualities.
典型的巴比妥类药物会产生一系列行为效应，包括抗惊厥、肌肉松弛、镇静催眠和抗焦虑作用。与这些典型的巴比妥类药物不同，存在一类巴比妥类药物具有惊厥作用，而非抗惊厥作用。这些惊厥性巴比妥类药物对焦虑相关行为的影响尚未得到研究。因此，本研究旨在比较惊厥性巴比妥类药物CHEB与多种典型巴比妥类药物在条件性饮水抑制（CSD）范式中的作用，该范式是一种用于研究焦虑和抗焦虑药物的“动物模型”。在每天10分钟的实验中，对缺水的大鼠进行训练，使其从偶尔通电（0.5 mA）的管子中饮水，通电由一个音调信号指示。在3 - 4周内，对照反应稳定下来（每次实验10 - 15次电击和10 - 15毫升水）；然后每周进行一次药物测试。与先前的报告一致，典型的巴比妥类药物（戊巴比妥、司可巴比妥、苯巴比妥）在不抑制背景反应（水摄入量）的剂量下，会使接受电击的次数产生剂量依赖性增加。相比之下，亚惊厥剂量的CHEB（0.3 - 2.5毫克/千克）会使受惩罚反应和背景反应都产生剂量依赖性降低。最后，发现用1.25毫克/千克的CHEB预处理不会改变戊巴比妥的抗冲突效应。这些结果表明：（1）惊厥性巴比妥类药物和典型巴比妥类药物对大鼠的冲突行为有明显不同的影响；（2）CHEB似乎不具有任何“巴比妥类拮抗剂”的特性。
