The effects of yohimbine on exploratory and locomotor behaviour are attributable to its effects at noradrenaline and not at benzodiazepine receptors.
A recent study has shown that the alpha 2-adrenoceptor antagonist, yohimbine, has an additional action, in micromolar concentrations, to inhibit the binding of [3H]benzodiazepines to their receptors in the CNS. An important question raised by this finding is to what extent the behavioural effects of yohimbine can be attributed to this action. Yohimbine (1.25-2.5 mg/kg) produced a dose-related decrease in exploratory head-dipping and locomotor activity in the holeboard test. The alpha 2-adrenoceptor agonist clonidine, in small doses (0.01-0.025 mg/kg), antagonized the reduction in exploratory head-dipping and locomotor activity produced by yohimbine (2.5 mg/kg). The benzodiazepine chlordiazepoxide (5-10 mg/kg), which reduces the activity of noradrenergic neurones, antagonized the effects of yohimbine less effectively. The inability of flumazepil (10-20 mg/kg; Ro 15-1788, a benzodiazepine receptor antagonist) to reverse the effects of yohimbine suggested that the low-affinity effect of yohimbine to displace the binding of benzodiazepines from their receptors, is not important in its behavioural effects in the holeboard, but that these effects are attributable to the alpha 2-antagonist action of yohimbine. These conclusions are consistent with previous results in an animal test of anxiety.
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D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001570:Benzodiazepinones / Q000008:administration & dosage; D002707:Chlordiazepoxide / Q000008:administration & dosage; D003000:Clonidine / Q000008:administration & dosage; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects*; D005442:Flumazenil; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects*; D015016:Yohimbine / Q000008:administration & dosage / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D001570:Benzodiazepinones; D011963:Receptors, GABA-A; D015016:Yohimbine; D005442:Flumazenil; D002707:Chlordiazepoxide; D003000:Clonidine