Cortical 5-HT1A receptor downregulation by antidepressants in rat brain

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 [H-3 ]5-HT and [H-3]8-OH-DPAT, respectively. It was observed that chronic exposu re to tricyclic antidepressants (TCAs) results in significant downregulatio n of total [H-3]5-HT binding sites in cortex (42-76%) and hippocampus (35-6 7%). 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 affi nity of [H-3]8-OH-DPAT was increased only with imipramine treatment both in cortex and hippocampus. The affinity of [H-3]5-HT to 5-HT binding sites in cortex was increased with imipramine treatment and decreased with desipram ine and clomipramine treatment. 5-HT sensitive adenylyl cyclase (AC) activi ty was significantly increased in cortex with imipramine (72%) and clomipra mine (17%) treatment, whereas in hippocampus only imipramine treatment sign ificantly increased AC activity (50%). In conclusion, chronic treatment wit h TCAs results in downregulation of cortical 5-HT1A receptors along with co ncomitant increase in 5-HT stimulated AC activity suggesting the involvemen t of cortical 5-HT1A receptors in the mechanism of action of TCAs. (C) 2001 Elsevier Science Ltd. All rights reserved.