Kamineni Institute of Medical Sciences, Sreepuram, Narketpally, Nalgonda 508254, Andhra Pradesh, India.
J Neural Transm (Vienna). 2010 Dec;117(12):1423-30. doi: 10.1007/s00702-010-0522-4. Epub 2010 Dec 7.
The aim of the present study was to examine the effect of chronic antidepressants treatment on the density of α₁-adrenoceptor (AR) subtypes in rat brain. Density of total α₁ and α(1A)- and α(1Β)-ARs was measured in cortex and cerebellum of rats treated with amitriptyline (AMI), desipramine (DMI) and fluoxetine (FLX), (10 mg/kg body wt), for 30 days, using [³H]prazosin in presence and absence of WB-4101. The density of cortical total α₁-ARs was significantly decreased with AMI (54%) and DMI (25%) treatment, without altering the affinity of the receptor. Fluoxetine did not alter the density of cortical α₁-ARs. The density of cortical α(1A)-ARs was also significantly decreased with AMI (85%) and DMI (50%) treatment, without affecting the affinity. The density of cerebellar total α₁-ARs was significantly decreased with AMI (37%), DMI (50%) and FLX (70%) treatment, without affecting the affinity for [³H]prazosin. The density of α(1A)-ARs was significantly decreased with AMI (67%), DMI (59%) and FLX (92%) treatment. α(1B)-AR density was decreased only with FLX (47%) and DMI (47%) treatment. Correspondingly the basal IP3 and NE (10 μM) stimulated IP3 levels were significantly decreased in AMI (47%), DMI (22%) and FLX (48%) treated rat cortex. The results suggest that chronic antidepressant (AD) treatment down-regulates the cortical and cerebellar total α₁-ARs in rat brain. However, α(1A) subtype is predominantly down-regulated by AMI and DMI, where as FLX affects cerebellar α(1A)-ARs. The region-specific and subtype specific down-regulation of α₁-ARs density, which occurs after prolonged AD treatment, may underline the therapeutic mechanism of action.
本研究旨在探讨慢性抗抑郁药物治疗对大鼠脑内α₁-肾上腺素能受体（AR）亚型密度的影响。采用[³H]哌唑嗪，在 WB-4101 存在和不存在的情况下，测量用阿米替林（AMI）、去甲丙咪嗪（DMI）和氟西汀（FLX）（10 mg/kg 体重）治疗 30 天的大鼠皮质和小脑总α₁和α(1A)-和α(1Β)-ARs 的密度。AMI（54%）和 DMI（25%）治疗显著降低皮质总α₁-AR 密度，而不改变受体的亲和力。氟西汀不改变皮质α₁-AR 密度。AMI（85%）和 DMI（50%）治疗也显著降低皮质α(1A)-AR 密度，而不影响亲和力。AMI（37%）、DMI（50%）和 FLX（70%）治疗显著降低小脑总α₁-AR 密度，而不影响[³H]哌唑嗪的亲和力。AMI（67%）、DMI（59%）和 FLX（92%）治疗显著降低α(1A)-AR 密度。仅 FLX（47%）和 DMI（47%）治疗降低α(1B)-AR 密度。相应地，AMI（47%）、DMI（22%）和 FLX（48%）治疗的大鼠皮质中基础 IP3 和 NE（10 μM）刺激的 IP3 水平显著降低。结果表明，慢性抗抑郁药（AD）治疗下调大鼠脑皮质和小脑总α₁-ARs。然而，AMI 和 DMI 主要下调α(1A)亚型，而 FLX 影响小脑α(1A)-ARs。AD 治疗后长期发生的α₁-ARs 密度的区域特异性和亚型特异性下调可能阐明其治疗作用机制。
