McNaughton N, Richardson J, Gore C
Neuroscience. 1986 Nov;19(3):899-903. doi: 10.1016/0306-4522(86)90306-4.
Anxiolytic drugs share many of the common behavioural effects of septal and hippocampal lesions in animals. Gray attributes this to changes which the anxiolytics produce in septal generation of hippocampal rhythmical slow activity. However, lesions of the dorsal ascending noradrenergic bundle reproduce this electrophysiological effect of the anxiolytics while only reproducing part of the behavioural profile of the anxiolytics. The present paper reports what appears to be a second common effect of anxiolytic drugs on the generation of hippocampal slow waves which could underlie their behavioural effects. Freely moving rats, previously implanted with electrodes, received high frequency electrical stimulation of the midbrain reticular formation to elicit hippocampal rhythmic slow activity. The frequency of the slow waves produced increased linearly with increasing stimulation intensity as has been reported previously. A barbiturate (amylobarbitone, 15 mg/kg, i.p.) and three benzodiazepines (chlordiazepoxide, 5 mg/kg; diazepam, 5 mg/kg; alprazolam, 1 mg/kg) all decreased the slope of the voltage-frequency function and decreased overall frequency of slow waves produced. Two antipsychotic drugs (haloperidol, 0.2 mg/kg; chlorpromazine, 2 mg/kg) produced similar behavioural sedation to the anxiolytics but did not decrease either the slope of the voltage-frequency function nor the overall frequency of slow waves. The results show that these barbiturates and benzodiazepines produce a common reduction in the frequency of hippocampal rhythmical slow activity. Given the importance attached to slow waves in current theories of hippocampal function, it is possible that this electrophysiological effect could have some relation to the behavioural effects of these anxiolytic drugs. If the effect can be shown to generalize to other classes of anxiolytic drug it could reflect changes in the substrate for the common effects of anxiolytic drugs on behaviour.
抗焦虑药物具有许多与动物中隔和海马损伤共同的行为效应。格雷将此归因于抗焦虑药物在海马节律性慢活动的中隔产生过程中所引起的变化。然而，背侧上行去甲肾上腺素能束的损伤再现了抗焦虑药物的这种电生理效应，却只再现了抗焦虑药物部分行为特征。本文报道了抗焦虑药物对海马慢波产生的另一种常见效应，这种效应可能是其行为效应的基础。先前已植入电极的自由活动大鼠接受中脑网状结构的高频电刺激，以引发海马节律性慢活动。如先前报道的那样，所产生的慢波频率随刺激强度增加呈线性增加。一种巴比妥酸盐（戊巴比妥，15毫克/千克，腹腔注射）和三种苯二氮䓬类药物（氯氮卓，5毫克/千克；地西泮，5毫克/千克；阿普唑仑，1毫克/千克）均降低了电压-频率函数的斜率，并降低了所产生慢波的总体频率。两种抗精神病药物（氟哌啶醇，0.2毫克/千克；氯丙嗪，2毫克/千克）产生了与抗焦虑药物类似的行为镇静作用，但既未降低电压-频率函数的斜率，也未降低慢波的总体频率。结果表明，这些巴比妥酸盐和苯二氮䓬类药物使海马节律性慢活动的频率普遍降低。鉴于当前海马功能理论中对慢波的重视，这种电生理效应可能与这些抗焦虑药物的行为效应存在某种关联。如果能证明这种效应可推广到其他类别的抗焦虑药物，那么它可能反映了抗焦虑药物对行为产生共同效应的底物变化。
