Cortical 5-HT1A receptor downregulation by antidepressants in rat brain |
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Authors: | B.N. Srinivas M.N. Subhash K.Y. Vinod |
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Affiliation: | a Department of Neurochemistry, National Institute of Mental Health and Neurosciences, P.B. No. 2900, Bangalore 560 029, India |
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Abstract: | Total 5-HT binding sites and 5-HT1A receptor density was measured in brain regions of rats treated with imipramine (5 mg/kg body wt), desipramine (10 mg/kg body wt) and clomipramine (10 mg/kg body wt), for 40 days, using [3H]5-HT and [3H]8-OH-DPAT, respectively. It was observed that chronic exposure to tricyclic antidepressants (TCAs) results in significant downregulation of total [3H]5-HT binding sites in cortex (42–76%) and hippocampus (35–67%). The 5-HT1A receptor density was, however, decreased significantly (32–60%) only in cortex with all the three drugs. Interestingly, in hippocampus imipramine treatment increased the 5-HT1A receptor density (14%). The affinity of [3H]8-OH-DPAT was increased only with imipramine treatment both in cortex and hippocampus. The affinity of [3H]5-HT to 5-HT binding sites in cortex was increased with imipramine treatment and decreased with desipramine and clomipramine treatment. 5-HT sensitive adenylyl cyclase (AC) activity was significantly increased in cortex with imipramine (72%) and clomipramine (17%) treatment, whereas in hippocampus only imipramine treatment significantly increased AC activity (50%). In conclusion, chronic treatment with TCAs results in downregulation of cortical 5-HT1A receptors along with concomitant increase in 5-HT stimulated AC activity suggesting the involvement of cortical 5-HT1A receptors in the mechanism of action of TCAs. |
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Keywords: | 5-HT1A receptors Tricyclic antidepressants Rat brain Chronic Adenylyl cyclase In vivo |
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