Chronic 5-HT2 receptor antagonist treatment alters 5-HT1A autoregulatory control of 5-HT release in rat brain in vivo.
Rats treated chronically (14 days) with the 5-HT2 receptor antagonist ritanserin, show decreased 5-HT2 receptor numbers in the frontal cortex. The present experiments were designed to investigate the effects of acute and chronic ritanserin treatment on the autoregulatory control of the release of 5-HT and its metabolite 5-HIAA in vivo in rats using intracerebral dialysis. Neither acute nor chronic ritanserin treatment altered basal extracellular levels of 5-HT or 5-HIAA, suggesting that 5-HT2 receptors do not directly influence 5-HT release. In the control animals, systemic stimulation of somatodendritic 5-HT1A receptors with the 5-HT1A receptor agonist 8-OH-DPAT, inhibited the release of 5-HT presumably via inhibitory feedback autoregulation; an effect also seen in animals treated acutely with ritanserin. However, in the animals treated chronically with ritanserin, administration of 8-OH-DPAT produced an initial increase in extracellular 5-HT which declined gradually to the end of the experiment. These results suggest that chronic, but not acute, 5-HT2 receptor antagonist treatment attenuates the 5-HT1A receptor-mediated autoregulation of 5-HT release. The underlying mechanisms have yet to be ascertained.
Department of Physiology and Pharmacology, Queen's Medical Centre, Nottingham, U.K.
E J
EJ
Kidd
J E
JE
Leysen
C A
CA
Marsden
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D016713:Ritanserin; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; D016713:Ritanserin; D006897:Hydroxyindoleacetic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin