Abstract
The effect of chronic administration of Imipramine on [3H]Spiperone binding to 5-HT2 sites and inositoltrisphosphate (IP3) levels in rat cerebral cortex was studied. Our data shows that treatment with imipramine (5 mg/kg body weight, intraperitoneally) for 30 days significantly down regulates 5-HT2 receptors sites (262 +/- 29 fmol/mg protein) in cerebral cortex (38%), compared to control rats (425 +/- 60 fmol/mg protein., P < 0.001). However there was no significant change in the affinity of [3H]-Spiperone binding (kd) to 5-HT2 sites in cerebral cortex after exposure to imipramine (Kd = 0.84 +/- 0.11 nM). It is also observed that imipramine treatment significantly reduces 5-HT stimulated [3H]IP3 formation in cerebral cortex (6,411 +/- 708 dpm/mg protein), compared to the saline treated rats (12,238 +/- 1,544 dpm/mg protein; P < 0.001), with concomitant decrease in Pdtlns-4-5-P2. This study suggests that the therapeutic action of imipramine in brain might be by reducing hypersensitivity of 5-HT2 receptors by down regulation, which leads to reduced levels of inositolphospholipids. This inturn reduces the levels of IP3. In conclusion, imipramine acts at presynaptic site by blocking the reuptake of serotonin and at post synaptic site it downregulates 5-HT2 sites with decreased IP3 levels after chronic exposure.
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