title: Alterations in extracellular and tissue levels of biogenic amines in rat brain induced by the serotonin2 receptor antagonist, ritanserin.
abstract: Systemic administration of ritanserin elicited rapid changes in dopamine (DA) and serotonin (5-HT) levels in both dialysate and neuronal tissue extracts. These effects occurred in both a site-selective and a dose-related manner. Increases in extracellular levels of DA and 5-HT in the nucleus accumbens were maximal at 120-140 min after treatment. A dose of 0.63 mg/kg of ritanserin elicited larger and more prolonged increases in extracellular DA and 5-HT levels than did the 0.3 mg/kg dose. By contrast, 0.63 mg/kg of ritanserin elicited no changes in either DA or 5-HT levels with dialysate collected from the striatum. Ritanserin also induced dose-related decreases in tissue levels of DA and 5-HT from the nucleus accumbens. The site specificity of action was again noted in that there were no dose-dependent decreases in tissue levels of DA or 5-HT measured from the striatum. Ritanserin exerted little effect on metabolite levels from either dialysate or tissue extracts. Taken together, these findings show that selective 5-HT2 receptor antagonism modulates DA and 5-HT neurotransmission in a specific manner. These actions appear to involve increased release of DA and 5-HT rather than significant changes in metabolism. These findings add further weight to the importance of 5-HT2 receptor interactions as an important component of antipsychotic activity.
authors.affiliation: Division of Pharmacology, Wellcome Research Laboratories, Research Triangle Park, North Carolina.
authors.forename: L L
authors.initials: LL
authors.lastname: Devaud
authors.forename: E B
authors.initials: EB
authors.lastname: Hollingsworth
authors.forename: B R
authors.initials: BR
authors.lastname: Cooper
mesh_terms: D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism*; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016713:Ritanserin / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists; D013997:Time Factors
chemical_list: D001679:Biogenic Amines; D012702:Serotonin Antagonists; D016713:Ritanserin; D012701:Serotonin; D004298:Dopamine