Yohimbine is a 5-HT1A agonist in rats in doses exceeding 1mg/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 100635. 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 1 mg/kg significantly activate these receptors.

Radioligand binding analysis of α2 adrenoceptors with [11C]yohimbine in brain in vivo: Extended Inhibition Plot correction for plasma protein binding

“…In contrast, challenge with RX821002 had the opposite effect on CBF. In rats, yohimbine is known to raise blood pressure and heart rate 24 , while the effect on CBF is unknown.…”

Pattern of neural activation following yohimbine‐induced reinstatement of alcohol seeking in rats

“…While yohimbine's anxiogenic activity is thought to be driven via activation of the adrenergic system, the exact mechanism by which yohimbine induces relapse is unknown. Yohimbine also acts as a 5‐HT 1A receptor agonist, but only at doses greater than 1 mg/kg (Zaretsky, Zaretskaia, DiMicco & Rusyniak, ). Furthermore, yohimbine's effect on reinstatement of food and cocaine seeking is not blocked by the α 2 ‐adrenoreceptor agonist clonidine (Nair et al., ), suggesting yohimbine is possibly acts via multiple systems to exert its effects.…”

Faster emergence behavior from ketamine/xylazine anesthesia with atipamezole versus yohimbine

“…Unlike ATI, which has a negligible affinity for serotonin (5-HT) [ 17 , 18 ], β 1 /β 2 -adrenergic, muscarinic, dopamine 2, tryptamine, GABA, opiate or benzodiazepine receptors [ 17 ], YOH is less discriminatory. High doses of YOH (>1 mg/kg; the current study used 4.3 mg/kg) have been shown to have 5-HT1A agonistic properties, which lead to decreases in heart rate, blood pressure, activity level, and body temperature [ 30 ]. Similarly, in doses approximating those used in the current study, YOH has been shown to decrease ambulation, an effect not seen with more selective α 2 -antagonists [ 19 ].…”

“…These differences are likely attributable to the differential affinity between the two drugs for α 2 -subtypes, as well as α 1 -interactions. Because the effects of adrenoceptor antagonism on behavior are dose-dependent [ 19 , 30 ], further experiments are needed to compare these results to lower doses of these drugs. During recovery from anesthesia it is difficult to determine if the animal is attempting to explore their environment versus exhibiting an escape response, however motoric behaviors can still be observed and measured.…”