Cortical alpha-adrenoceptor downregulation by tricyclic antidepressants in the rat brain |
| |
Authors: | Subhash M N Nagaraja M R Sharada S Vinod K Y |
| |
Institution: | Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Post Box No. 2900, Bangalore 560029, India |
| |
Abstract: | The aim of the present study was to examine the effect of chronic tricyclic antidepressants (TCAs) treatment on the density of -adrenoceptors in the rat brain. Density of 1- and 2-adrenoceptors was measured in cortex and hippocampus of rats treated with imipramine (IMI, 5 mg/kg body weight), desipramine (DMI, 10 mg/kg body weight), clomipramine (CMI, 10 mg/kg body weight) and amitriptyline (AMI, 10 mg/kg body weight), for 40 days, using 3H]prazosin and 3H]clonidine, respectively. The density of cortical 1-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 2-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 1-adrenoceptors was significantly decreased only with AMI treatment (47%), without affecting the affinity for 3H]prazosin. However, no change in hippocampal 2-adrenoceptor density was observed with any of these TCAs. The results suggest that chronic antidepressant (AD) treatment downregulates the cortical, but not hippocampal, 1- and 2-adrenoceptors in rat brain. The region-specific downregulation of 1- and 2-adrenoceptors density, which occur after prolonged AD treatment, may underline the therapeutic mechanism of action. |
| |
Keywords: | Alpha-adrenoceptors Tricyclic antidepressants Rat brain [3H]Prazosin [3H]Clonidine |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|