Role of 5-HT2A and 5-HT2B/2C receptors in the behavioral interactions between serotonin and catecholamine reuptake inhibitors

Lance R. McMahon, Kathryn A. Cunningham

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


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-HT2A receptor antagonist M100907 (2 mg/kg) and potentiated by the 5-HT2B/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-HT2A receptors; whereas, 5-HT2B/2C receptors may serve to limit this effect. Thus, the balance of activation between 5-HT2A and 5-HT2B/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.

Original languageEnglish (US)
Pages (from-to)319-329
Number of pages11
Issue number3
StatePublished - 2001


  • 5-HT Receptors
  • 5-HT Receptors
  • Dopamine
  • Locomotor activity
  • Serotonin

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health


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