Lista A, Blier P, de Montigny C
Department of Psychiatry, McGill University, Montréal, Québec, Canada.
J Pharmacol Exp Ther. 1990 Jul;254(1):318-23.
In the present electrophysiological studies the effects of the activation of putative presynaptic benzodiazepine receptors (BZR) in modulating serotonergic (5-HT) transmission in dorsal hippocampus were investigated in chloral hydrate-anesthetized rats. The effectiveness of the electrical stimulation of the ascending 5-HT pathway on the firing activity of CA3 hippocampus pyramidal neurons was modulated by the intravenous administration of BZR ligands. The BZR agonists, diazepam, lorazepam and CL 218,872, dose-dependently enhanced the effectiveness of the stimulation. In contrast, the BZR inverse agonist, FG 7142, dose-dependently decreased it. The effects of agonist and inverse agonist BZR ligands were blocked by the specific BZR antagonist flumazenil. Diazepam and FG 7142 did not modify the efficacy of microiontophoretic applications of gamma-aminobutyric acid and 5-HT onto hippocampal CA3 neurons. BMY 7378, a 5-HT1A receptor antagonist which blocks the effect of the endogenous 5-HT released by the electrical stimulation of 5-HT fibers in this paradigm, also blocked the enhancing action of diazepam on the effectiveness of the stimulation. These results indicate that the activation of BZR of type I modulates 5-HT neurotransmission, presumably through a presynaptic regulatory mechanism.
在本电生理研究中，我们在水合氯醛麻醉的大鼠中研究了假定的突触前苯二氮䓬受体（BZR）激活对背侧海马中5-羟色胺能（5-HT）传递的调节作用。通过静脉注射BZR配体来调节5-HT上行通路电刺激对CA3海马锥体神经元放电活动的有效性。BZR激动剂地西泮、劳拉西泮和CL 218,872剂量依赖性地增强了刺激的有效性。相反，BZR反向激动剂FG 7142剂量依赖性地降低了刺激的有效性。激动剂和反向激动剂BZR配体的作用被特异性BZR拮抗剂氟马西尼阻断。地西泮和FG 7142并未改变γ-氨基丁酸和5-HT微离子透入海马CA3神经元的效力。BMY 7378是一种5-HT1A受体拮抗剂，在此范式中可阻断5-HT纤维电刺激释放的内源性5-HT的作用，它也阻断了地西泮对刺激有效性的增强作用。这些结果表明，I型BZR的激活可能通过一种突触前调节机制来调节5-HT神经传递。
