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Title of Journal: J Neural Transm

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Abbravation: Journal of Neural Transmission

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Springer Vienna

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DOI

10.1016/0306-4522(89)90339-4

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1435-1463

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Differential modulation of alpha1 adrenoceptor su

Authors: D Ramakrishna M N Subhash
Publish Date: 2010/12/07
Volume: 117, Issue: 12, Pages: 1423-1430
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Abstract

The aim of the present study was to examine the effect of chronic antidepressants treatment on the density of α1adrenoceptor AR subtypes in rat brain Density of total α1 and α1A and α1ΒARs 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 3Hprazosin in presence and absence of WB4101 The density of cortical total α1ARs 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 α1ARs The density of cortical α1AARs was also significantly decreased with AMI 85 and DMI 50 treatment without affecting the affinity The density of cerebellar total α1ARs was significantly decreased with AMI 37 DMI 50 and FLX 70 treatment without affecting the affinity for 3Hprazosin The density of α1AARs was significantly decreased with AMI 67 DMI 59 and FLX 92 treatment α1BAR 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 downregulates the cortical and cerebellar total α1ARs in rat brain However α1A subtype is predominantly downregulated by AMI and DMI where as FLX affects cerebellar α1AARs The regionspecific and subtype specific downregulation of α1ARs density which occurs after prolonged AD treatment may underline the therapeutic mechanism of actionThis study was supported by the Indian Council of Medical Research New Delhi Project No 9800140 We thank Kamineni Institute of Medical Sciences for constant encouragement and support to publish this work and Dr Pragna Rao for reviewing the draft article

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