Cortical alpha-adrenoceptor downregulation by tricyclic antidepressants in the rat brain

• Published in: Neurochemistry international 2003-12, Vol.43 (7), p.603-609
• Main Authors: Subhash, M.N, Nagaraja, M.R, Sharada, S, Vinod, K.Y
• Format: Article
• Language: English
• Subjects: [ [formula omitted]]Clonidine; [ [formula omitted]]Prazosin; Alpha-adrenoceptors; Amitriptyline - pharmacology; Animals; Antidepressive Agents, Tricyclic - pharmacology; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Clomipramine - pharmacology; Desipramine - pharmacology; Dose-Response Relationship, Drug; Down-Regulation; Fundamental and applied biological sciences. Psychology; Hippocampus - drug effects; Hippocampus - metabolism; Imipramine - pharmacology; In Vitro Techniques; Male; Medical sciences; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Radioligand Assay; Rat brain; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, alpha-1 - metabolism; Receptors, Adrenergic, alpha-2 - metabolism; Time Factors; Tricyclic antidepressants; Vertebrates: nervous system and sense organs
• ISSN: 0197-0186; 1872-9754
• 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 α-adrenoceptors in the rat brain. Density of α 1- and α 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 [ 3 H ]prazosin and [ 3 H ]clonidine, respectively. The density of cortical α 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 α 2-adrenoceptors was also significantly decreased with DMI (69%), CMI (81%) and AMI (80%) treatment, without affecting the affinity for [ 3 H ]clonidine. The density of hippocampal α 1-adrenoceptors was significantly decreased only with AMI treatment (47%), without affecting the affinity for [ 3 H ]prazosin. However, no change in hippocampal α 2-adrenoceptor density was observed with any of these TCAs. The results suggest that chronic antidepressant (AD) treatment downregulates the cortical, but not hippocampal, α 1- and α 2-adrenoceptors in rat brain. The region-specific downregulation of α 1- and α 2-adrenoceptors density, which occur after prolonged AD treatment, may underline the therapeutic mechanism of action.