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 alpha 2-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 alpha 2-adrenoceptor agonist, clonidine (30-100 micrograms 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 micrograms 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 micrograms 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 micrograms 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 micrograms 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.
Cheng
C H
CH
Postgraduate Studies in Pharmacology, School of Pharmacy, University of Bradford, West Yorkshire.
Costall
B
B
Ge
J
J
Naylor
R J
RJ
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism*; D003000:Clonidine / Q000494:pharmacology; D003956:Dialysis; D003975:Diazepam / Q000494:pharmacology; D004347:Drug Interactions; D005110:Extracellular Space / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D017294:Ondansetron / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D001549:Benzamides; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D012702:Serotonin Antagonists; D015016:Yohimbine; D012701:Serotonin; D017294:Ondansetron; D006897:Hydroxyindoleacetic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C055971:zacopride; D003000:Clonidine; D003975:Diazepam