Citation

Ramakrishna D, Subhash MN. J. Neural. Transm. 2010; 117(12): 1423-1430.

Copyright

(Copyright © 2010, Holtzbrinck Springer Nature Publishing Group)

DOI

10.1007/s00702-010-0522-4

PMID

unavailable

Abstract

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 α1A- and α1Β-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 α1A-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 α1A-ARs was significantly decreased with AMI (67%), DMI (59%) and FLX (92%) treatment. α1B-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, α1A subtype is predominantly down-regulated by AMI and DMI, where as FLX affects cerebellar α1A-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.

Language: en