Curet O, De Montigny C, Blier P
Department of Psychiatry, McGill University, Montreal, Quebec, Canada.
Eur J Pharmacol. 1992 Oct 6;221(1):59-70. doi: 10.1016/0014-2999(92)90772-v.
The present electrophysiological experiments were undertaken to investigate the effect of desipramine and d-amphetamine on noradrenergic neurotransmission in the rat central nervous system. The effectiveness of electrical stimulation of the locus coeruleus and of microiontophoretic application of norepinephrine (NE) in suppressing the firing activity of CA3 pyramidal neurons was studied in the dorsal hippocampus. Desipramine (0.5 and 5 mg/kg i.v.) and d-amphetamine (0.25 and 5 mg/kg i.v.) decreased the effectiveness of locus coeruleus stimulation and prolonged the effect of microiontophoretically applied NE on the same pyramidal neurons. Subsequent i.v. administration of idazoxan, an alpha 2-adrenoceptor antagonist, reversed the effects of desipramine and d-amphetamine on the effectiveness of locus coeruleus stimulation and decreased that of microiontophoretically applied NE. In addition, idazoxan prevented the effect of subsequent administration of desipramine (5 mg/kg i.v.) on the effectiveness of locus coeruleus stimulation. High doses of d-amphetamine (5 and 10 mg/kg i.v.) decreased the firing activity of hippocampus pyramidal neurons by 70 and 98%, respectively, whereas low doses of desipramine (0.5 mg/kg i.v.) or of d-amphetamine (0.25 mg/kg i.v.) were without effect. After lesioning of NE projections with 6-hydroxydopamine, the effect of the 5 mg/kg dose of d-amphetamine on the firing activity of hippocampus pyramidal neurons was markedly reduced, whereas the cumulative 10 mg/kg dose of d-amphetamine completely suppressed, as in control rats, the firing activity of these neurons. This effect of d-amphetamine in 6-hydroxydopamine-pretreated rats was reversed by the administration of the 5-HT1A receptor antagonist BMY 7378. These data provide evidence that acute administration of desipramine and d-amphetamine decreases the effectiveness of locus coeruleus stimulation by increasing the activation of terminal alpha 2-adrenoceptor autoreceptors. In addition, acute administration of high doses of d-amphetamine decreases the firing rate of hippocampus pyramidal neurons by increasing NE and serotonin release.
进行了当前的电生理实验，以研究去甲丙咪嗪和右旋苯丙胺对大鼠中枢神经系统中去甲肾上腺素能神经传递的影响。在背侧海马体中，研究了电刺激蓝斑以及微量离子电泳应用去甲肾上腺素（NE）对抑制CA3锥体神经元放电活动的有效性。去甲丙咪嗪（静脉注射0.5和5mg/kg）和右旋苯丙胺（静脉注射0.25和5mg/kg）降低了蓝斑刺激的有效性，并延长了微量离子电泳应用NE对相同锥体神经元的作用。随后静脉注射α2肾上腺素能受体拮抗剂咪唑克生，逆转了去甲丙咪嗪和右旋苯丙胺对蓝斑刺激有效性的影响，并降低了微量离子电泳应用NE的影响。此外，咪唑克生还阻止了随后静脉注射去甲丙咪嗪（5mg/kg）对蓝斑刺激有效性的影响。高剂量的右旋苯丙胺（静脉注射5和10mg/kg）分别使海马锥体神经元的放电活动降低了70%和98%，而低剂量的去甲丙咪嗪（静脉注射0.5mg/kg）或右旋苯丙胺（静脉注射0.25mg/kg）则没有效果。在用6-羟基多巴胺损伤NE投射后，5mg/kg剂量的右旋苯丙胺对海马锥体神经元放电活动的影响明显降低，而累积10mg/kg剂量的右旋苯丙胺则像在对照大鼠中一样完全抑制了这些神经元的放电活动。在6-羟基多巴胺预处理的大鼠中，右旋苯丙胺的这种作用被5-HT1A受体拮抗剂BMY 7378的给药所逆转。这些数据提供了证据，表明急性给予去甲丙咪嗪和右旋苯丙胺通过增加终末α2肾上腺素能受体自身受体的激活来降低蓝斑刺激的有效性。此外，急性给予高剂量的右旋苯丙胺通过增加NE和5-羟色胺的释放来降低海马锥体神经元的放电率。
