title: Role of 5-HT(2a) and 5-HT(2B/2C) receptors in the behavioral interactions between serotonin and catecholamine reuptake inhibitors.
abstract: Dysfunction of monoamine neurotransmission seems to contribute to such pathopsychological states as depression, schizophrenia, and drug abuse. The present study examined the effects of the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) and antidepressant fluvoxamine on locomotor activity in rats following administration of the catecholamine reuptake inhibitor mazindol. Mazindol (1 mg/kg) did not alter locomotor activity; whereas, fluvoxamine (20 mg/kg) given alone induced a brief period of hypomotility. Hyperactivity was elicited in a dose-related manner when fluvoxamine (5-20 mg/kg) was combined with mazindol (1 mg/kg). The hyperactivity elicited by fluvoxamine (20 mg/kg) plus mazindol (1 mg/kg) was significantly attenuated by the 5-HT(2A) receptor antagonist M100907 (2 mg/kg) and potentiated by the 5-HT(2B/2C) receptor antagonist SB 206553 (2 mg/kg). Neither antagonist significantly altered basal activity. The hyperactivity evoked by the combination of fluvoxamine and mazindol seems to be mediated in part by 5-HT(2A) receptors; whereas, 5-HT(2B/2C) receptors may serve to limit this effect. Thus, the balance of activation between 5-HT(2A) and 5-HT(2B/2C) receptors seems to contribute to the expression of locomotor hyperactivity evoked via combination of a 5-HT and a catecholamine reuptake inhibitor. A disruption in this balance may contribute to the expression of affective disorders, schizophrenia, and drug abuse.
authors.affiliation: Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: L R
authors.initials: LR
authors.lastname: McMahon
authors.forename: K A
authors.initials: KA
authors.lastname: Cunningham
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D015306:Biogenic Monoamines / Q000378:metabolism; D002395:Catecholamines / Q000502:physiology*; D003863:Depression / Q000209:etiology / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D004357:Drug Synergism; D005464:Fluorobenzenes / Q000494:pharmacology; D016666:Fluvoxamine / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008454:Mazindol / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000502:physiology*; D012559:Schizophrenia / Q000209:etiology / Q000473:pathology; D012701:Serotonin / Q000502:physiology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D019966:Substance-Related Disorders / Q000209:etiology / Q000473:pathology
chemical_list: D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D002395:Catecholamines; D004298:Dopamine; D005464:Fluorobenzenes; D016666:Fluvoxamine; D007211:Indoles; D008454:Mazindol; D010880:Piperidines; D011725:Pyridines; D044402:Receptor, Serotonin, 5-HT2A; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; C094868:SB 206553; C079049:volinanserin