Differences in enhancing effects of zolpidem and benzodiazepine drugs on recurrent inhibition in rat hippocampal slices

It has been reported that the clinical and electroencephalographic profiles of zolpidem, a non-benzodiazepine drug which binds preferentially to the ω₁ benzodiazepine recognition sites located within the GABA_A receptor complex, are different from those of benzodiazepine drugs, which bind non-selectively to the ω₁ and ω₂ sites. In order to clarify the electrophysiological mechanism underlying the unique profile of zolpidem, the present study compared the enhancing effects of zolpidem and two benzodiazepine drugs, triazolam and diazepam, on recurrent inhibition. This inhibition was expressed as suppression of the orthodromically induced population spikes by the preceding antidromic stimulation of the alveus in the CA1 region of rat hippocampal slices. The rank order of potency for enhancing recurrent inhibition was triazolam > diazepam > zolpidem. From the present results and previously reported findings that zolpidem has a lower affinity for the ω₂ sites than diazepam while both have the same affinity for the ω₁ sites, we concluded that the hippocampal recurrent inhibition appears to be enhanced mainly by activation of the ω₂ sites, but not by that of the ω₁ sites. Furthermore, the lower potency of zolpidem for enhancing recurrent inhibition may underlie its unique profile in terms of its clinical and electroencephalographic effects. Received: 1 November 1996/Final version: 22 January 1997     

红景天镇静催眠作用的实验研究

目的探讨中药红景天(Rhodiola rosea)的镇静催眠作用。方法取雄性SD大鼠30只,设正常对照组(不灌服任何药物)、阴性对照组(灌服羧甲基纤维素钠溶液)、地西泮组(灌服地西泮溶液)、红景天低剂量组(灌服低剂量红景天)、红景天中剂量组(灌服中剂量红景天)和红景天高剂量组(灌服高剂量红景天),每组5只。灌服药物1h后,各组动物按照55mg/kg的剂量腹腔注射0.1%戊巴比妥钠溶液,记录每只大鼠从腹腔注射戊巴比妥钠到翻正反射消失的时间为睡眠潜伏期,翻正反射消失的到翻正反射开始出现的时间为睡眠时间,观察灌服不同剂量红景天对大鼠睡眠潜伏期及睡眠时间的影响。结果与正常对照组(3.24±0.22、93.96±2.25)相比,灌服中剂量及高剂量的红景天可以缩短大鼠的睡眠潜伏期(2.42±0.33,P<0.01;2.16±0.13,P<0.01),亦可延长大鼠的睡眠时间(102.54±3.15,P<0.05;107.10±7.75,P<0.05)。结论中剂量及高剂量的的红景天对大鼠具有镇静催眠作用。     

氧化槐定碱对小鼠中枢神经系统的影响

目的 探讨氧化槐定碱对中枢神经系统的影响。方法 采用行为药理学方法观察并测定氧化槐定碱对阈剂量和阈下剂量戊巴比妥催眠作用的影响,对小鼠外观活动和自身活动的影响及对戊四氮惊厥的影响。结果 腹腔内注射氧化槐定碱250,500,1000mg/kg,小鼠自发活动抑制率分别为42．6％,57．2％和76．3％,戊巴比妥钠入睡时间分别缩短38．4％,49．0％和39．7％,而睡眠时间分别延长172％,138％和389％,并能明显加强阈下剂量戊巴比妥钠的催眠作用。氧化槐定碱500,1000mg/kg不能对抗戊四氮引的惊厥。结论 氧化槐定碱具有镇静、催眠等中枢抑制作用。     

Alcohol Acceptance, Preference, and Sensitivity in Mice. II. Quantitative Trait Loci Mapping Analysis Using BXD Recombinant Inbred Strains

Quantitative trait loci (QTL) mapping of complex phenotypes has emerged as an important feature of the recombinant inbred (Rl) strain methodology. In this second study of our series on alcohol-related behaviors in mice, we examine alcohol acceptance, preference, and hypnotic dose sensitivity (HDS) to a standard dose of alcohol measured in BXD RI strains to identify candidate QTL regions responsible for their heritability. We detected highly significant marker associations for acceptance on chromosome 12 (Eif4e) , for preference on chromosome 1 (D1Rti2) and chromosome 7 (D7Mit7) , and for HDS on chromosome 7 (Mpmv1). These are the strongest QTL associations that we detected, but several other candidate QTL regions are reported. Given the limited number of BXD RI strains available, the large number of markers used herein, and the consequent chance of identifying false marker associations, these RI QTL mapping results must be seen as tentative, but an important first step toward identifying QTL for alcohol-related behaviors.     

“That's not my arm”: A hypnotic analogue of somatoparaphrenia

Introduction. “Instrumental hypnosis” allows researchers to model clinical symptoms in the laboratory, creating “virtual patients” with reversible disturbances in, for example, perception, action, memory, or belief. We used hypnosis to temporarily recreate somatoparaphrenia, a delusional belief that one's own limb belongs to someone else.

Methods. We compared a “Fully Formed” somatoparaphrenia suggestion with a “Factor 1 + Factor 2” suggestion that attempted to generate the delusional belief from analogues of its hypothesised underlying factors (i.e., paralysis plus disrupted critical belief evaluation). We tested and then challenged subjects’ responses to these suggestions.

Results. Although many hypnotic subjects experienced temporary paralysis, only a minority claimed their arm did not belong to them. Notably, the Fully Formed suggestion was more successful in recreating features of somatoparaphrenia than the Factor 1 + Factor 2 suggestion. In response to the challenges, some of those who developed temporary somatoparaphrenia maintained their belief throughout the hypnosis session.

Conclusions. We discuss these findings in terms of the “two-factor” theory of delusions and we highlight the advantages versus disadvantages of using hypnosis to explore such delusional beliefs in the laboratory.     

柏子养心丸镇静催眠作用实验研究

目的:考察柏子养心丸对小鼠的镇静催眠作用。方法:采用戊巴比妥钠对小鼠睡眠的协同作用方法。结果:柏子养心丸可明显延长阈上剂量戊巴比妥纳所致小鼠睡眠时间,增加阈下剂量戊巴比妥钠睡眠动物数。结论: 提示柏子养心丸具有镇静催眠作用。     

伪麻黄碱水杨酸对小鼠中枢作用的研究

目的 了解伪麻黄碱水杨酸对小鼠中枢神经系统的作用。方法 采用行为药理学实验观察伪麻黄碱水杨酸对小鼠一般行为、自主活动、对戊巴比妥钠诱导睡眠潜伏期、睡眠持续时间以及戊四氮、烟碱和印防己毒素诱导惊厥作用的影响。结果 12．5、25．0、50．0、100．0mg／kg伪麻黄碱水杨酸腹腔注射后,小鼠外观行为表现为兴奋,但自主活动被抑制;以上4个剂量的伪麻黄碱水杨酸可显著抑制戊巴比妥钠诱导的催眠作用;100．0mg／kg伪麻黄碱水杨酸对戊四氮、烟碱及印防己毒素诱导的惊厥具有协同作用。结论 伪麻黄碱水杨酸对小鼠中枢具有兴奋作用。     

Delusions of alien control in the normal brain

Delusions of alien control, or passivity experiences, are symptoms associated with schizophrenia in which patients misattribute self-generated actions to an external source. In this study hypnosis was used to induce a similar misattribution of self-generated movement in normal, healthy individuals. Positron Emission Tomography (PET) was employed to investigate the neural correlates of active movements correctly attributed to the self, compared with identical active movements misattributed to an external source. Active movements attributed to an external source resulted in significantly higher activations in the parietal cortex and cerebellum than identical active movements correctly attributed to the self. We suggest that, as a result of hypnotic suggestion, the functioning of this cerebellar-parietal network is altered so that self-produced actions are experienced as being external. These results have implications for the brain mechanisms underlying delusions of control, which may be associated with overactivation of the cerebellar-parietal network.     

Effects of daytime administration of zolpidem versus triazolam on memory

To determine whether zolpidem (an imidazopyridine hypnotic) produces amnestic effects which are similar to those produced by triazolam (a benzodiazepine hypnotic), 70 subjects were administered either triazolam (0.125, 0.25, or 0.5 mg), zolpidem (5, 10 or 15 mg) or placebo, then tested on Simulated Escape, Restricted Reminding, and Paired-Associates memory tests at 1.5 hours post-dosing (i.e., near the time of estimated peak blood concentration for both drugs) and again at 6 hours post-dosing. Triazolam 0.5 mg produced the greatest memory impairment at both test times, and also produced the greatest degree of sedation during intervening daytime naps in a non-sleep-conducive environment. Other doses of triazolam and zolpidem produced less memory impairment, but also failed to significantly enhance sleep. The results are consistent with the view that the amnestic and hypnotic effects of these sleep-inducing medications are functionally coupled.