Nazar M, Siemiatkowski M, 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):369-81. doi: 10.1007/s007020050165.
The effects of an intrahippocampal administering of a nonselective full (midazolam), a partial benzodiazepine (BDZ) receptor agonist (bretazenil), and a BDZ1 selective (zolpidem) receptor ligand were examined in the open field test (OFT) of neophobia and Vogel's test (VT) of conflict behavior in rats. Moreover, the influence of local injections of a noncompetitive GABA(A) receptor antagonist, picrotoxin, on the anxiolytic-like effect of serotonin (5-HT) depletion (p-chlorophenylalanine, p-CPA) in the Vogel test was studied. It was found that in the OFT only midazolam (0.1 microg/site) given to the hippocampus (HP) disinhibited rat exploratory behavior, whereas all the examined compounds inhibited animal motor activity when injected locally at 10.0 microg/site, the highest dose used in the tests. In the VT, again, only midazolam disinhibited rat conflict behavior on a dose-dependent basis. Picrotoxin administered to the HP produced a tendency to increase locomotor activity in rats, and significantly attenuated the anti-conflict action of serotonin depletion without changing the pain threshold and spontaneous drinking of the animals. p-CPA induced potent, dose-dependent and selective 5-HT and 5-hydroxyindoleacetic acid decrease in the HP after administering the dose used in the behavioral experiment. Thus, the present data provide evidence for the lack of selective anxiolytic activity of a partial non-selective agonist and a full selective agonist at the BDZ1 receptor after their administration to the HP. The model of intra-HP drug injections appeared effective in discriminating the anxiolytic spectrum of activity of new psychotropic compounds. Moreover, the obtained results indicate that the dorsal HP is one of the central sites important for GABA/5-HT interaction that modulates rat emotional behavior.
在大鼠的新物体恐惧旷场试验（OFT）和冲突行为的Vogel试验（VT）中，研究了海马内注射非选择性完全苯二氮䓬类药物（咪达唑仑）、部分苯二氮䓬（BDZ）受体激动剂（布雷替奈）和BDZ1选择性受体配体（唑吡坦）的效果。此外，还研究了局部注射非竞争性GABA(A)受体拮抗剂印防己毒素对Vogel试验中5-羟色胺（5-HT）耗竭（对氯苯丙氨酸，p-CPA）的抗焦虑样作用的影响。结果发现，在OFT中，仅海马（HP）给予咪达唑仑（0.1微克/位点）可解除对大鼠探索行为的抑制，而当以10.0微克/位点（试验中使用的最高剂量）局部注射时，所有受试化合物均抑制动物运动活性。在VT中，同样只有咪达唑仑能剂量依赖性地解除对大鼠冲突行为的抑制。向HP注射印防己毒素使大鼠有运动活性增加的趋势，并显著减弱5-HT耗竭的抗冲突作用，而不改变动物的痛阈和自发饮水。在行为实验中使用相应剂量给药后，p-CPA可使HP中5-HT和5-羟吲哚乙酸呈强效、剂量依赖性和选择性降低。因此，目前的数据证明，部分非选择性激动剂和完全选择性激动剂在给予HP后，在BDZ1受体缺乏选择性抗焦虑活性。HP内注射药物的模型似乎可有效区分新型精神药物的抗焦虑活性谱。此外，所得结果表明，背侧HP是调节大鼠情绪行为的GABA/5-HT相互作用的重要中枢位点之一。
