血清素耗竭对大鼠在Vogel试验中的行为及脑内3H-唑吡坦结合的影响。

Nazar M, Siemiatkowski M, Bidziński A, Członkowska A, Sienkiewicz-Jarosz H, Płaźnik A

Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Warsaw, Poland.

J Neural Transm (Vienna). 1999;106(5-6):355-68. doi: 10.1007/s007020050164.

The influence of p-chlorophenylalanine (p-CPA) and 5,7-dihydroxytryptamine (5,7-DHT)-induced serotonin depletion on rat behavior as well as on zolpidem's the behavioral effects and binding to some brain areas of zolpidem, was examined with the help of Vogel's punished drinking test and autoradiography, respectively. Moreover, changes in the serotonin levels and turnover rate were studied in the forebrain and brainstem of rats pretreated with various ligands at the benzodiazepine (BDZ) receptors (midazolam, bretazenil, abecarnil, zolpidem). These drugs were given at doses shown previously to significantly disinhibit animal behavior suppressed by punishment in the Vogel test (Nazar et al., 1997). It was found that serotonin decrease in the frontal cortex and hippocampus after p-CPA significantly and inversely correlated with rat behavior controlled by fear in the VT. p-CPA produced an anticonflict activity in the absence of effect on spontaneous drinking, pain threshold and motility of animals. All applied benzodiazepine receptor ligands decreased the 5-HT turnover rate in the frontal cortex and hippocampus, whereas in the brainstem only abecarnil and zolpidem diminished 5-hydroxyindoleacetic acid levels. This part of the study replicated earlier data with neurotoxins and indicated that the anxiolytic-like effect of 5-HT depletion in some models of anxiety did not depend on changes in animal appetitive behavior or stimulus control. Moreover, the fact that all nonselective and selective (zolpidem) agonists of the type 1 benzodiazepine receptors seemed to produce the same anticonflict effect and decreasing 5-HT turnover indicates that this subtype of benzodiazepine receptor may be important for the interaction between brain 5-HT and GABA/BDZ systems. Accordingly, it was found that serotonin decrease enhanced the anticonflict effect of zolpidem in the Vogel test and increased 3H-zolpidem binding to the occipital cortex and substantia nigra. Altogether, the present study provides more arguments for the role of changes in the activity of brain 5-HT innervation in the control of emotional processes. Moreover, it points to the BDZ1 receptor subtype as a possible target of interaction between brain 5-HT and GABA(A)/BDZ systems.

分别借助Vogel惩罚性饮水试验和放射自显影技术，研究了对氯苯丙氨酸（p-CPA）和5,7-二羟基色胺（5,7-DHT）诱导的血清素耗竭对大鼠行为的影响，以及对唑吡坦行为效应和与大鼠某些脑区结合的影响。此外，还研究了用苯二氮䓬（BDZ）受体的各种配体（咪达唑仑、布雷替奈、阿贝卡尼、唑吡坦）预处理的大鼠前脑和脑干中血清素水平和周转率的变化。这些药物的给药剂量如先前所示，能显著解除Vogel试验中因惩罚而抑制的动物行为（Nazar等人，1997年）。结果发现，p-CPA处理后额叶皮质和海马体中的血清素减少与VT中受恐惧控制的大鼠行为显著负相关。p-CPA在不影响动物自发饮水、痛阈和运动能力的情况下产生抗冲突活性。所有应用的苯二氮䓬受体配体均降低了额叶皮质和海马体中的5-羟色胺周转率，而在脑干中只有阿贝卡尼和唑吡坦降低了5-羟吲哚乙酸水平。该研究部分重复了早期用神经毒素得到的数据，表明在某些焦虑模型中，5-羟色胺耗竭的抗焦虑样效应不依赖于动物食欲行为或刺激控制的变化。此外，1型苯二氮䓬受体的所有非选择性和选择性（唑吡坦）激动剂似乎产生相同的抗冲突效应并降低5-羟色胺周转率，这一事实表明该亚型苯二氮䓬受体可能对脑5-羟色胺与GABA/BDZ系统之间的相互作用很重要。因此，发现在Vogel试验中血清素减少增强了唑吡坦的抗冲突效应，并增加了3H-唑吡坦与枕叶皮质和黑质的结合。总之，本研究为脑5-羟色胺神经支配活动变化在情绪过程控制中的作用提供了更多论据。此外，它指出BDZ1受体亚型可能是脑5-羟色胺与GABA(A)/BDZ系统之间相互作用的靶点。