DIFFERENTIAL EFFECT OF ANTIDEPRESSANTS ON Gqα -PROTEIN LEVELS IN RAT BRAIN

Abstract

Heterotrimeric G proteins play a pivotal role in post receptor information transduction. These proteins have been implicated in the pathophysiology, diagnosis, and treatment of depression. Aims and Objectives: The aim of the present study was to examine the effect of chronic antidepressants treatment on the Gqα-protein levels in rat brain.  Density of Gqα/11α-protein levels was measured in cortex and cerebellum of rats treated with amitriptyline (AMI), desipramine (DMI) and fluoxetine (FLX) and imipramine (10 mg/Kg body wt), for 30 days, using Sodium Dodecyl Sulphate – Polyacrylamide Gel Electrophoresis (SDS-PAGE) and western blotting.  In cortex, a significant decrease was observed after AMI treatment (28%, p<0.0001), followed by DMI (17%, p<0.0001) and CMI (19%, p<0.0001). In contrast a significant increase was observed after IMI treatment (14%, p<0.001) but there was no change in fluoxetine treatment. In cerebellum, a significant increase in Gqprotein levels was observed after treatment with all the above drugs. A very high increase was observed after CMI treatment (114%, p<0.0001) as compared to AMI (59%, p<0.0001), DMI (45%, p<0.0001) fluoxetine (28%, p<0.0001) and IMI (42%, p<0.0001).  The results suggest that chronic antidepressant (AD) treatment decreases the expression of cortical Gqα/11α-protein levels in contrast to cerebellum where these proteins are showed increased expression. However IMI treatment in cortical Gqα/11αprotein levels predominantly over expressed by IMI treatment. The region-specific expression of Gqα/11α-protein levels which occurs after prolonged AD treatment, may underline the therapeutic mechanism of action.