Bergstrom D A, Kellar K J
J Pharmacol Exp Ther. 1979 May;209(2):256-61.
The effects of chronic administration of the tricyclic antidepressant agent desmethylimipramine (DMI) on brain adrenergic and serotonergic receptor binding processes were studied. We examined the kinetic properties of alpha adrenergic, beta adrenergic and serotonergic receptor binding sites in cortical and subcortical brain regions of rats treated chronically for various time periods with DMI(6 mg/kg i.p. daily). After 1 week of daily injections, beta receptor binding density in the cortex was significantly decreased. The reduced density of the cortical beta receptors was evident throughout a 12-week administration period. It was not until after 6 weeks of DMI administration that a significant reduction in the subcortical beta receptors was evident. Compared to saline-injected controls, chronic DMI administration lowered [3H]dihydroalprenolol binding in the hippocampus but not in the striatum. After 12 weeks of DMI we detected no differences in alpha adrenergic binding characteristics in the cortex or subcortical forebrain using [3H]dihydroergocryptine as the binding ligand. There was no consistent alteration in the cortical serotonin receptor densities throughout the 12 weeks of DMI administration, and DMI had no effect on the serotonergic binding characteristics in the subcortical forebrain region. We conclude that chronic DMI administration selectively decreases the density of beta adrenergic receptors in rat brain.
研究了长期给予三环类抗抑郁药去甲丙咪嗪（DMI）对脑内肾上腺素能和5-羟色胺能受体结合过程的影响。我们检测了用DMI（每天腹腔注射6mg/kg）长期处理不同时间段的大鼠皮质和皮质下脑区中α肾上腺素能、β肾上腺素能和5-羟色胺能受体结合位点的动力学特性。每日注射1周后，皮质中的β受体结合密度显著降低。在整个12周的给药期内，皮质β受体密度的降低都很明显。直到DMI给药6周后，皮质下β受体才出现明显的显著降低。与注射生理盐水的对照组相比，长期给予DMI可降低海马中[3H]二氢心得安的结合，但对纹状体无影响。DMI处理12周后，使用[3H]二氢麦角隐亭作为结合配体，我们未检测到皮质或皮质下前脑α肾上腺素能结合特性的差异。在DMI给药的12周内，皮质5-羟色胺受体密度没有持续变化，且DMI对皮质下前脑区的5-羟色胺能结合特性没有影响。我们得出结论：长期给予DMI可选择性降低大鼠脑中β肾上腺素能受体的密度。
