title: A microdialysis study of ST1936, a novel 5-HT6 receptor agonist.
abstract: The function of 5-HT6 receptors, one of the last additions to the large family of 5-HT receptors, is largely unknown due to the limited knowledge of their transduction mechanisms, lack of full centrally acting agonists and inconsistencies in the pharmacological and neurochemical effects of the antagonists. Recently, a new full agonist, ST1936, with nanomolar affinity for 5-HT6 receptors, has become available. Here we report the effect of ST1936 (5-10-20 mg/kg/ip) on dialysate DA, NA and 5-HT in the medial prefrontal cortex (PFCX) and in the shell and core of the nucleus accumbens (NAc). Systemic administration of ST1936 dose-dependently increased dialysate DA and NA in the NAc shell and PFCX and to a lesser extent in the NAc core; these effects were prevented by systemic administration of the two 5-HT6 receptor antagonists, SB271046 (10-20 mg/kg/ip) and SB399885 (5 mg/kg/ip). These properties of ST1936 suggest that 5-HT6 receptors control the activity of DA and NA neurons projecting to the NAc and to the PFCX.
authors.affiliation: Department of Toxicology, University of Cagliari, Cagliari, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Valentini
authors.forename: R
authors.initials: R
authors.lastname: Frau
authors.forename: F
authors.initials: F
authors.lastname: Bordi
authors.forename: F
authors.initials: F
authors.lastname: Borsini
authors.forename: G
authors.initials: G
authors.lastname: Di Chiara
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005021:Ethylamines / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology
chemical_list: C558115:2-(5-chloro-2-methyl-1H-indol-3-yl)-N,N-dimethylethanamine; D005021:Ethylamines; D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; D013876:Thiophenes; C097216:serotonin 6 receptor; D012701:Serotonin; C117443:SB 271046; D004298:Dopamine; D009638:Norepinephrine