Evidence for antiserotonergic properties of yohimbine

Linda P. Dwoskin, Bethany S. Neal, Sheldon B. Sparber

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Yohimbine (YOH) is a widely used pharmacological tool employed to produce a selective blockade of alpha2-adrenergic receptors. In the present study operant behavior was used as a biobehavioral assay to determine the activity of YOH at serotonergic receptors, as indicated by its ability to antagonize the behavioral effects of a serotonergic agonist, lysergic acid diethylamide (LSD). Rats were trained to respond on a Fixed Ratio 15 schedule for food reinforcement. YOH (0.5-5.0 mg/kg) or vehicle and LSD (50 μg/kg) were administered (IP) 30 min and immediately prior, respectively, to the 30-min operant session. In a separate study, the ability of YOH (0.5-2.5 mg/kg) to antagonize a higher dose of LSD (100 μg/kg) was examined. Relatively low doses of YOH (0.5-1.0 mg/kg) were able to partially, but significantly antagonize the LSD-induced suppression and typical hallucinogen-induced disruption of schedule-controlled responding. These results suggest that YOH, even at moderate doses, may act nonselectively as an antagonist at 5-HT receptors, in addition to its antagonist action at alpha2-adrenergic receptors. This study demonstrates the utility of operant behavior as a biobehavioral assay to study the receptor mediated action of drugs.

Original languageEnglish
Pages (from-to)321-326
Number of pages6
JournalPharmacology Biochemistry and Behavior
Issue number2
StatePublished - Oct 1988

Bibliographical note

Funding Information:
The interaction of YOH with 5-HT function was examined in the present study by determining its ability to antagonize the behavioral effect of 5-HT receptor agonist lysergic IThis work was supported iri part by U.S.P.H.S. grants DA 00532, GM 07397 and MH42934. sPresent address: College of Pharmacy, University of Kentucky, Rose Street, Pharmacy Build/ng, Lexington, KY 40536-0082. 8Requests for reprints should be addressed to Sheldon B. Sparber.


  • Lysergic acid diethylamide
  • Operant behavior
  • Serotonin
  • Yohimbine

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience


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