The profiles of interaction of yohimbine with anxiolytic and putative anxiolytic agents to modify 5‐HT release in the frontal cortex of freely‐moving rats

Abstract

The interaction of yohimbine with anxiolytic and putative anxiolytic agents to modify 5‐hydroxytryptamine (5‐HT) release in the frontal cortex of the freely‐moving rat was assessed using the microdialysis technique. The α2‐adrenoceptor antagonist, yohimbine (5.0 mg kg−1, i.p.) increased maximally the extracellular levels of 5‐HT in the rat frontal cortex by approximately 230% of the basal levels. The α2‐adrenoceptor agonist, clonidine (30–100 μg kg−1, i.p.) decreased dose‐dependently the extracellular levels of 5‐HT in the rat frontal cortex by approximately 0–60% of the basal levels. A 5 min pretreatment with clonidine (50 μg kg−1, i.p.) prevented the yohimbine‐induced increase in the extracellular 5‐HT levels. The benzodiazepine receptor agonist, diazepam (2.5 mg kg−1, i.p.) and the 5‐HT3 receptor antagonist, ondansetron (100 μg kg−1, i.p.) (5 min pretreatment) completely prevented the yohimbine (5.0 mg kg−1, i.p.)‐induced increases in the extracellular levels of 5‐HT. The 5‐HT1A receptor agonist, 8‐OH‐DPAT (0.32 mg kg−1, s.c.) partially antagonized the yohimbine response. A 5 min pretreatment with the 5‐HT3/5‐HT4 receptor ligand R(+)‐zacopride (10 μg kg−1, i.p.) reversed the yohimbine (5.0 mg kg−1, i.p.)‐induced increase in the extracellular levels of 5‐HT to approximately 30% below the basal levels. A 5 min pretreatment with S(−)‐zacopride (100 μg kg−1, i.p.) failed to modify the response to yohimbine. The present study provides evidence of the ability of the anxiogenic agent, yohimbine, to increase the activity of the central 5‐hydroxytryptaminergic system and the ability of clonidine and various anxiolytic and putative anxiolytic agents to prevent the yohimbine response. 1993 British Pharmacological Society