title: Yohimbine is a 5-HT1A agonist in rats in doses exceeding 1 mg/kg.
abstract: Yohimbine is a prototypical alpha2-adrenergic receptor antagonist. Due to its relatively high selectivity, yohimbine is often used in experiments whose purpose is to examine the role of these receptors. For example, yohimbine has been employed at doses of 1-5 mg/kg to reinstate drug-seeking behavior after extinction or to antagonize general anesthesia, an effects presumably being a consequence of blocking alpha2-adrenergic receptors. In this report we characterized dose-dependent autonomic and behavioral effects of yohimbine and its interaction with an antagonist of 5-HT1A receptors, WAY 100,635. In low doses (0.5-2 mg/kg i.p.) yohimbine induced locomotor activation which was accompanied by a tachycardia and mild hypertension. Increasing the dose to 3-4.5 mg/kg reversed the hypertension and locomotor activation and induced profound hypothermia. The hypothermia as well as the suppression of the locomotion and the hypertension could be reversed by the blockade of 5-HT1A receptors with WAY 100635. Our data confirm that yohimbine possesses 5-HT1A properties, and demonstrated that in doses above 1mg/kg significantly activate these receptors.
authors.affiliation: Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN 46202 USA. Electronic address: dzaretsk@iu.edu.
authors.forename: Dmitry V
authors.initials: DV
authors.lastname: Zaretsky
authors.affiliation: Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN 46202 USA.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Zaretskaia
authors.affiliation: Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: DiMicco
authors.affiliation: Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN 46202 USA; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Rusyniak
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D058825:Serotonin 5-HT1 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D015016:Yohimbine / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D010879:Piperazines; D011725:Pyridines; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D015016:Yohimbine; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
keywords: 5-HT1A receptors; Body temperature; Locomotor activity; Yohimbine