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

1 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. 2 The alpha2-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. 3 The alpha2-adrenoceptor agonist, clonidine (30-100 mug 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 mug kg-1, i.p.) prevented the yohimbine-induced increase in the extracellular 5-HT levels. 4 The benzodiazepine receptor agonist, diazepam (2.5 mg kg-1, i.p.) and the 5-HT3 receptor antagonist, ondansetron (100 mug 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. 5 A 5 min pretreatment with the 5-HT3/5-HT4 receptor ligand R(+)-zacopride (10 mug kg-1, i.p.) reversed the yohimbine (5.O 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 mug kg-1, i.p.) failed to modify the response to yohimbine. 6 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.