Effect of established and putative anxiolytics on extracellular 5-HT and 5-HIAA in the ventral hippocampus of rats during behaviour on the elevated X-maze.
One of the proposed mechanisms of action for the anxiolytic effects of the benzodiazepines is via a decrease in central serotonergic neurotransmission. The aim of this study was to combine in vivo microdialysis in the rat with behaviour on the elevated X-maze to determine changes in 5-HT release in the ventral hippocampus with concomitant measurement of behaviour. Twenty minutes exposure to the elevated X-maze resulted in an increase in extracellular 5-HT in the ventral hippocampus with no change in extracellular 5-HIAA. Restricting the rat to either the open or the closed arms produced an increase in extracellular 5-HT, however the increase in 5-HT when restricted to the open arms was not significantly greater than that on the closed arms. Forty minutes pretreatment with diazepam (2.5 mg kg-1 IP) significantly inhibited the increase in extracellular 5-HT in the ventral hippocampus and had an anxiolytic profile over 5 min and 20 min exposures of the rats to the X-maze. Diazepam had no effect on basal 5-HT levels before exposure to the X-maze but reduced extracellular 5-HT levels when the animal was returned to the holding cage. Forty minutes pretreatment with the .5-HT1A receptor partial agonist ipsapirone (1 mg kg-1 IP) significantly inhibited the increase in extracellular 5-HT in the ventral hippocampus but did not produce behaviour different from vehicle controls after 5 or 20 min periods on the X-maze.(ABSTRACT TRUNCATED AT 250 WORDS)
Wright
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Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham, UK.
Upton
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Marsden
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CA
D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology; D006624:Hippocampus / Q000737:chemistry / Q000187:drug effects*; D006897:Hydroxyindoleacetic Acid / Q000032:analysis*; D008297:Male; D017551:Microdialysis; D011724:Pyridazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000032:analysis*
D014151:Anti-Anxiety Agents; D011724:Pyridazines; D011743:Pyrimidines; C077138:F 2692; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C043077:ipsapirone; D003975:Diazepam