Department of Psychology and Neuroscience Research Centre, University of Otago, Dunedin, New Zealand.
J Psychopharmacol. 1995 Jan;9(4):326-30. doi: 10.1177/026988119500900406.
Buspirone is a novel anxiolytic which does not share the muscle relaxant, anticonvulsant and sedative properties of classical anxiolytics such as the benzodiazepines. Its effects on behavioural tests of anxiolytic action generally match those of classical anxiolytics provided a low dose is used. However, in a previous experiment, buspirone appeared to affect fixed interval responding in a way which differed qualitatively as well as quantitatively from the classical anxiolytic chlordiazepoxide. It takes as much as 2 weeks for the clinical effects of anxiolytics to develop, during which time the side effects of benzodiazepines undergo tolerance. We, therefore, decided to compare long-term pre-administration (60 days, three injections/day) of buspirone and chlordiazepoxide on learning of a fixed interval 60-s schedule. The doses were based on previous acute dose-response tests of hippocampal theta rhythm in freely moving animals. Buspirone (0.1 mg/ kg i.p.) and chlordiazepoxide (0.4 mg/kg i.p.) produced similar increases in responding, especially in the middle of acquisition of the fixed interval schedule. Consistent with our acute electrophysiological tests, the effects of 0.4 mg/kg chlordiazepoxide were somewhat larger than those of 0.1 mg/kg buspirone. These results suggest that the acute effects of buspirone, but probably not chlordiazepoxide, on fixed interval responding are contaminated by side effects which do not seriously affect the results with long-term administration. The effects of both novel and classical anxiolytics on control of hippocampal theta rhythm appear to predict the magnitude of their common anxiolytic effects and to be unrelated to their different side effects.
丁螺环酮是一种新型的抗焦虑药物，它不具有苯二氮䓬类等经典抗焦虑药物的肌肉松弛、抗惊厥和镇静作用。在使用低剂量的情况下，它在行为学抗焦虑测试中的作用通常与经典抗焦虑药物的作用相匹配。然而，在之前的一项实验中，丁螺环酮似乎以一种与经典抗焦虑药物氯氮䓬不同的质和量的方式影响固定间隔反应。抗焦虑药物的临床效果需要 2 周的时间才能显现，在此期间，苯二氮䓬类药物的副作用会产生耐受性。因此，我们决定比较丁螺环酮和氯氮䓬的长期预先给药（60 天，每天 3 次注射）对固定间隔 60 秒方案的学习的影响。剂量基于以前对自由活动动物海马θ节律的急性剂量反应测试。丁螺环酮（0.1mg/kg，腹腔注射）和氯氮䓬（0.4mg/kg，腹腔注射）都能显著增加反应，特别是在固定间隔方案的中期。与我们的急性电生理测试结果一致，0.4mg/kg 氯氮䓬的作用比 0.1mg/kg 丁螺环酮的作用略大。这些结果表明，丁螺环酮的急性作用，但可能不是氯氮䓬，对固定间隔反应的影响可能受到副作用的污染，而这些副作用不会严重影响长期给药的结果。新型和经典抗焦虑药物对海马θ节律的控制作用似乎可以预测它们共同的抗焦虑作用的大小，并且与它们不同的副作用无关。
