Characterization of serotonin receptors and lack of effect of antidepressant therapy on monoamine functions in various regions of the rabbit brain.
The effects of single and long-term administration of the antidepressants imipramine, desimipramine, amitriptyline, zimelidine and maprotiline were studied in the rabbit brain. Special attention was given to the brain serotonin (5-HT) receptors. Our results show that in different areas of the rabbit brain, the binding sites for 5-HT display pharmacological characteristics very similar to those of the 5-HT1 and 5-HT2 receptors described for the rat brain. No significant correlation could be shown between the distribution of either of the receptors and the distribution of serotonergic nerve terminals (as measured by the 5-HT content and the [3H]5-HT accumulation). Addition of antidepressants to rabbit brain slices, in vitro, caused an inhibition of the [3H]5-HT accumulation. The compounds only weakly inhibited the binding of [3H]5-HT and [3H]ketanserin as compared to the inhibition caused by serotonergic agonists and antagonists. The [3H]5-HT accumulation in brain slices was markedly reduced 2 h after a single i.p. injection of imipramine. After a two-week administration of the antidepressants, the specific binding of neither [3H]5-HT nor [3H]ketanserin was significantly altered. The simultaneous determination of monoamine metabolites and of dopamine-beta-hydroxylase in the cerebrospinal fluid of these treated rabbits did not reveal any significant difference from the control animals.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001679:Biogenic Amines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D066298:In Vitro Techniques; D007650:Ketanserin / Q000378:metabolism; D007700:Kinetics; D011817:Rabbits; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D014018:Tissue Distribution
D000928:Antidepressive Agents; D001679:Biogenic Amines; D011985:Receptors, Serotonin; D007650:Ketanserin; D004299:Dopamine beta-Hydroxylase