Subhash M N, Nagaraja M R, Sharada S, Vinod K Y
Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Post Box No. 2900, Bangalore 560029, India.
Neurochem Int. 2003 Dec;43(7):603-9. doi: 10.1016/s0197-0186(03)00097-4.
The aim of the present study was to examine the effect of chronic tricyclic antidepressants (TCAs) treatment on the density of alpha-adrenoceptors in the rat brain. Density of alpha1- and alpha2-adrenoceptors was measured in cortex and hippocampus of rats treated with imipramine (IMI, 5mg/kg body weight), desipramine (DMI, 10mg/kg body weight), clomipramine (CMI, 10mg/kg body weight) and amitriptyline (AMI, 10mg/kg body weight), for 40 days, using [3H]prazosin and [3H]clonidine, respectively. The density of cortical alpha1-adrenoceptors was significantly decreased with IMI (46%), DMI (21%), CMI (50%) and AMI (67%) treatment, without altering the affinity of the receptor. The density of cortical alpha2-adrenoceptors was also significantly decreased with DMI (69%), CMI (81%) and AMI (80%) treatment, without affecting the affinity for [3H]clonidine. The density of hippocampal alpha1-adrenoceptors was significantly decreased only with AMI treatment (47%), without affecting the affinity for [3H]prazosin. However, no change in hippocampal alpha2-adrenoceptor density was observed with any of these TCAs. The results suggest that chronic antidepressant (AD) treatment downregulates the cortical, but not hippocampal, alpha1- and alpha2-adrenoceptors in rat brain. The region-specific downregulation of alpha1- and alpha2-adrenoceptors density, which occur after prolonged AD treatment, may underline the therapeutic mechanism of action.
本研究的目的是检测慢性三环类抗抑郁药（TCA）治疗对大鼠脑内α-肾上腺素能受体密度的影响。分别使用[3H]哌唑嗪和[3H]可乐定，测定用丙咪嗪（IMI，5mg/kg体重）、地昔帕明（DMI，10mg/kg体重）、氯米帕明（CMI，10mg/kg体重）和阿米替林（AMI，10mg/kg体重）治疗40天的大鼠皮质和海马中α1-和α2-肾上腺素能受体的密度。IMI（46%）、DMI（21%）、CMI（50%）和AMI（67%）治疗可使皮质α1-肾上腺素能受体密度显著降低，而不改变受体亲和力。DMI（69%）、CMI（81%）和AMI（80%）治疗也可使皮质α2-肾上腺素能受体密度显著降低，而不影响对[3H]可乐定的亲和力。仅AMI治疗（47%）可使海马α1-肾上腺素能受体密度显著降低，而不影响对[3H]哌唑嗪的亲和力。然而，这些TCA中的任何一种均未观察到海马α2-肾上腺素能受体密度的变化。结果表明，慢性抗抑郁药（AD）治疗可下调大鼠脑内皮质而非海马的α1-和α2-肾上腺素能受体。长期AD治疗后出现的α1-和α2-肾上腺素能受体密度的区域特异性下调可能是其治疗作用机制的基础。
