Evidence for antiserotonergic properties of yohimbine.
Yohimbine (YOH) is a widely used pharmacological tool employed to produce a selective blockade of alpha 2-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 micrograms/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 micrograms/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 alpha 2-adrenergic receptors. This study demonstrates the utility of operant behavior as a biobehavioral assay to study the receptor mediated action of drugs.
Dwoskin
L P
LP
Department of Pharmacology and Psychiatry, Medical School University of Minnesota, Minneapolis 55455.
Neal
B S
BS
Sparber
S B
SB
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008238:Lysergic Acid Diethylamide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology*
D011985:Receptors, Serotonin; D015016:Yohimbine; D008238:Lysergic Acid Diethylamide