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

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Abstract
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. Ipsapirone 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 novel anxiolytic F2692 (10 mg kg−1 IP) significantly inhibited the increase in extracellular 5-HT in the ventral hippocampus and had an anxiolytic profile over the 5 min but not the 20 min period when the rat was on the X-maze. F2692 reduced basal extracellular 5-HT levels both 20 min before exposure to the X-maze and when the animal was returned to the holding cage. The results are discussed based on the effects of these compounds on basal and elevated extracellular 5-HT levels and their behavioural profile on the X-maze.