Selective destruction of the serotonergic fibers of the fornix-fimbria and cingulum bundle increases 5-HT1 but not 5-HT2 receptors in rat midbrain.
Selected and localized lesions of serotonergic (5-HT) neurons were made by microinjection of 5,7-dihydroxytryptamine (5,7-DHT), after pretreatment with desipramine, into the cingulum bundle and fornix-fimbria; these are the major serotonergic hippocampal inputs from the median raphe nucleus. Two weeks after the lesion, the binding of [3H]5-HT (5-HT1 receptor) was determined in the hippocampus which receives the afferent terminals and, in addition, in the septum/hypothalamus and midbrain from where the fibers originate. Scatchard analysis showed there was no significant change in binding parameters in the hippocampus; however, a significant increase was observed in the Bmax in the midbrain (38%) with no change in the KD. The caudate which receives 5-HT inputs via other 5-HT tracts was not affected by the lesion. The changes in 5-HT1 receptor number or affinity were not observed 6 days or 5 weeks after the lesion. The binding of the ligands [3H]spiroperidol and [3H]ketanserin to the 5-HT2 receptor population was also determined in the same brain areas; no changes in receptor binding occurred two weeks after the lesion. These experiments demonstrate that a selective lesion of the serotonergic system can increase 5-HT1 receptors in the midbrain, which contains the serotonin cell bodies. In addition, as 5-HT2 binding is not altered, this further supports the hypothesis that 5-HT1 and 5-HT2 receptors are distinct populations of receptors.
D015116:5,7-Dihydroxytryptamine / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000502:physiology*; D004102:Dihydroxytryptamines / Q000633:toxicity*; D006624:Hippocampus / Q000502:physiology; D007031:Hypothalamus / Q000502:physiology; D008297:Male; D008636:Mesencephalon / Q000502:physiology; D008845:Microinjections; D009412:Nerve Fibers / Q000502:physiology; D009474:Neurons / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism*; D012686:Septal Nuclei / Q000502:physiology; D012701:Serotonin / Q000378:metabolism*
D004102:Dihydroxytryptamines; D011985:Receptors, Serotonin; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin