The effects of tricyclic antidepressant on the presynaptic and postsynaptic noradrenergic neurotransmission were studied at various times during chronic administation of imipramine in rats. The purpose of this experiment was to investigate the therap...
The effects of tricyclic antidepressant on the presynaptic and postsynaptic noradrenergic neurotransmission were studied at various times during chronic administation of imipramine in rats. The purpose of this experiment was to investigate the therapeutic mechanism of imipramine. The leels of MHPG in cerebral cortex as the index of presynaptic noradrenergic activity were measured by high performance liquid chromatography with electrochemical detector (HPLC-ECD). Postsynaptic beta-adrenergic receptors of cerebral cortex were assayed by ³H-dihydroalprenolol(³H-DHA) ligand bindings.
The results were as follows :
1) The level of MHPG at cerebral cortex was decreased (statistically not significant) by the short term(1 day) treatment of imiprmine. However a statistically significant increase was noted by the long term administration(3 weeks) in comparison to controls.
2) The number of maximal binding sites(Bmax) of cerebral beta-adrenergic receptors was reduced significantly compared to the controls after a 5 weeks administration without significant concomitant change in the receptor affinity(Kd).
3) Although a strong negative correlation was noted between the change in MHPG level and beta-adrenergic receptor numbers(Bmax) in cerebral cortex, this was found to be statistically insignificant.
In summary, long term administration of imipramine enhanced the presynaptic noradrenergic activity and reduced postsynaptic beta adrenergic receptor numbers. And these findings were thought to be related with the therapeutic mechanism of imipramine.