Cortical alpha-adrenoceptor downregulation by tricyclic antidepressants in the rat brain.
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.
Subhash
M N
MN
Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Post Box No. 2900, Bangalore 560029, India. subhash@nimhans.kar.nic.in
Nagaraja
M R
MR
Sharada
S
S
Vinod
K Y
KY
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002997:Clomipramine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D013997:Time Factors
D000929:Antidepressive Agents, Tricyclic; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D000639:Amitriptyline; D002997:Clomipramine; D007099:Imipramine; D003891:Desipramine