Effect of central nervous system-acting drugs after selective destruction by neurotoxins of 5-hydroxytryptamine fibers in the brain.
Some behavioral effects of CNS-acting drugs have been studied in two animal species after functional impairment of central serotonergic activity. In rabbits, pretreatment with p-CPA or with 5,6-DHT counteracted the hyperthermia induced by d-amphetamine or apomorphine; the same pretreatments were ineffective in modifying pyrogen-induced fever. These data indicate a modulatory role of the 5-HT system in the hyperthermic response to dopaminergic agonists, such as d-amphetamine and apomorphine, and rule out 5-HT involvement in the hyperpyrexia induced by pyrogen. A previous intraventricular injection of 5,6-DHT significantly potentiated the increase in body temperature induced by 5-HTP in combination with a MAO inhibitor. Pretreatment with p-CPA, instead, strongly inhibited the hyperthermic response to 5-HTP. In unanesthetized fowl, at the time of the most dramatic degenerative signs of indoleaminergic neurons induced by 5,6-DHT, as documented by histofluorescence pictures, intraventricular infusion of 5-HT induced more intense behavioral, electrocortical, and body temperature modifications than in control animals. These results suggest the existence of receptor supersensitivity after 5-HT nerve ending degeneration but not after brain 5-HT depletion. The hyperthermic effect of a presynaptically acting drug, fenfluramine, was counteracted in rabbits and in fowl pretreated with either p-CPA or 5,6-DHT. Since identical behavioral, electrocortical, and body temperature effects have been observed after 5-HT or 5,6-DHT infusion into the third ventricle of fowl, it may be concluded that 5,6-DHT behaves also as a central 5-HT receptor agonist.
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001679:Biogenic Amines / Q000378:metabolism; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002491:Central Nervous System Agents / Q000494:pharmacology*; D002645:Chickens; D005277:Fenfluramine / Q000494:pharmacology; D008297:Male; D009412:Nerve Fibers / Q000187:drug effects* / Q000502:physiology; D011749:Pyrogens / Q000494:pharmacology; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D001679:Biogenic Amines; D002491:Central Nervous System Agents; D011749:Pyrogens; D012702:Serotonin Antagonists; D005277:Fenfluramine; D012701:Serotonin; D006916:5-Hydroxytryptophan; D001058:Apomorphine