Effects of the selective norepinephrine reuptake inhibitor reboxetine on norepinephrine and serotonin transmission in the rat hippocampus

被引:51
作者
Szabo, ST [1 ]
Blier, P
机构
[1] Univ Florida, Inst Brain, Dept Psychiat, Gainesville, FL 32610 USA
[2] McGill Univ, Neurobiol Psychiat Unit, Montreal, PQ H3A 1A1, Canada
关键词
antidepressants; alpha(2)-adrenoceptors; clonidine; 5-HT1A receptors; 5-HT1B receptors; locus coeruleus;
D O I
10.1016/S0893-133X(01)00284-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Given that norepinephrine (NE) and scrotonin (5-HT) neurons arc implicated in the mechanisms of action of antidepressant drugs and both project to the hippocampus, the impact of acute and long-term administration of the selective NE inhibitor reboxetine was assessed oil CA(3) pyramidal neuron firing in this postsynaptic structure. Cumulative injections of reboxetine (1-4 mg/kg, i.v.) dose-dependently increased the recovery time of the firing of these neurons following iontophoretic applications of NE, but not 5-HT. In rats treated with reboxetine for 2.5 mg/kg/day for 21 days, a robust increase in the recovery time following NE applications was observed, and a small but significant prolongation occurred following 5-HT applications. In controls and reboxetine-treated rats, 1 and 5 Hz stimulations of the afferent 5-HT bundle to the hippocampus, which allows determination of terminal 5-HT1B autoreceptor sensitivity, produced similar frequency-dependent decreases in pyramidal neuron firing in both groups. However, after low and high doses of clonidine (10 and 400 mug/kg, i.v.), which assesses alpha (2)-adrenergic auto- and heteroreceptor sensitivity, respectively, only the effect of the high dose of clonidine was attenuated. Interestingly, administration of the selective 5-HT1A receptor antagonist WAY 100,635 induced a 140% increase in basal pyramidal neuron firing in reboxetine as compared to saline-treated rats. This increase in tonic activation of postsynaptic 5-HT1A receptors might be attributable in part to a desensitization of alpha (2)-adrenergic heteroreceptors, presumably resulting from sustained NE reuptake inhibition. These results indicate that even a selective NE reuptake inhibitor can modulate 5-HT transmission. [Neuropsychopharmacology 25:845-857,2001 (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.
引用
收藏
页码:845 / 857
页数:13
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