title: Melatonin agonists modulate 5-HT2A receptor-mediated neurotransmission: behavioral and biochemical studies in the rat.
abstract: Interactions between melatonin and serotonin type 2A (5-HT2A) receptors in the regulation of the sleep-wakefulness cycle in the rat have been reported. We studied the acute effects of melatonin and related agonists on 5-HT2A neurotransmission as reflected in behavioral (head shake) and biochemical [phosphoinositide (PI) hydrolysis] responses to 5-HT2A receptor stimulation. Like 5-HT1A agonists and antidepressants, acute administration of melatonin and related agonists inhibited the 5-HT2A-mediated (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane-induced head shake in a dose-dependent manner. Consistent with these behavioral findings, in vitro incubation of cortical slices with melatonin agonists robustly inhibited 5-HT2A receptor-mediated PI hydrolysis in a noncompetitive manner. 2-Iodomelatonin-induced reductions in 5-HT2A-stimulated PI hydrolysis were blocked by preincubation with the melatonin antagonist N-acetyltryptamine. Further, pretreatment of rats in vivo with melatonin and related agonists reduced the cortical PI hydrolysis response to the 5-HT2A agonist alpha methyl-5-HT but did not alter cortical 5-HT2A receptor density. The present data support an interaction between melatonin and 5-HT2A receptors in the central nervous system.
authors.affiliation: CNS Developmental Pharmacology, Pharmaceutical Research Institute, Bristol-Myers Squibb Company, Wallingford, Connecticut, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Eison
authors.forename: R P
authors.initials: RP
authors.lastname: Freeman
authors.forename: V B
authors.initials: VB
authors.lastname: Guss
authors.forename: U L
authors.initials: UL
authors.lastname: Mullins
authors.forename: R N
authors.initials: RN
authors.lastname: Wright
mesh_terms: D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D006868:Hydrolysis; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D000662:Amphetamines; D010716:Phosphatidylinositols; D011985:Receptors, Serotonin; D008550:Melatonin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine