Zhu X O, McNaughton N
Department of Psychology, University of Otago, Dunedin, New Zealand.
Psychopharmacology (Berl). 1995 Mar;118(1):93-100. doi: 10.1007/BF02245254.
In free-moving male rats, the function relating frequency to the threshold current required to drive hippocampal rhythmical slow activity (RSA; "theta") with septal stimulation has a minimum at 7.7 Hz. Classical anxiolytics all increase thresholds in the region of 7.7 Hz, and so does the novel anxiolytic buspirone. However, unlike classical anxiolytics, 2 or 3 weeks are normally required for the onset of the clinical effects of buspirone. This study tested the effects of long-term administration of chlordiazepoxide and buspirone on septal driving of RSA. Separate groups of naive rats received three IP injections per day of chlordiazepoxide (0.4 mg/kg), buspirone (0.1 mg/kg) or saline for 50 days. Both chlordiazepoxide and buspirone increased thresholds at 7.7 Hz, as expected. These acute effects were not significantly changed with chronic administration. Buspirone and chlordiazepoxide produced similar, statistically significant, but small cumulative reductions in thresholds at 6.9 Hz. The present experiments suggest that if the effects of anxiolytic drugs on septally driven RSA provide any basis for their clinical action, then classical anxiolytics may have two actions: an immediate effect on euphoria and tension and a delayed effect on anxiety proper--with buspirone sharing only the latter effect.
在自由活动的雄性大鼠中，将频率与通过隔区刺激驱动海马节律性慢活动（RSA；“θ波”）所需的阈电流相关联的函数在7.7Hz时具有最小值。经典抗焦虑药均会提高7.7Hz区域的阈电流，新型抗焦虑药丁螺环酮也有同样的作用。然而，与经典抗焦虑药不同，丁螺环酮的临床效果通常需要2至3周才会显现。本研究测试了长期给予氯氮卓和丁螺环酮对隔区驱动RSA的影响。将单独的几组未用药大鼠每天腹腔注射氯氮卓（0.4mg/kg）、丁螺环酮（0.1mg/kg）或生理盐水，持续50天。正如预期的那样，氯氮卓和丁螺环酮均提高了7.7Hz时的阈电流。这些急性效应在长期给药后并未显著改变。丁螺环酮和氯氮卓在6.9Hz时产生了相似的、具有统计学意义但幅度较小累积阈电流降低。目前的实验表明，如果抗焦虑药物对隔区驱动的RSA的影响为其临床作用提供了任何依据，那么经典抗焦虑药可能有两种作用：对欣快感和紧张感的即时作用以及对真正焦虑的延迟作用——而丁螺环酮仅具有后者的作用。
