EFFECT OF ESTABLISHED AND PUTATIVE ANXIOLYTICS ON EXTRACELLULAR 5-HT AND 5-HIAA IN THE VENTRAL HIPPOCAMPUS OF RATS DURING BEHAVIOR ON THE ELEVATED X-MAZE

被引:117
作者
WRIGHT, IK [1 ]
UPTON, N [1 ]
MARSDEN, CA [1 ]
机构
[1] SMITHKLINE BEECHAM,MED RES CTR,HARLOW CM19 5AD,ESSEX,ENGLAND
关键词
MICRODIALYSIS; 5-HT; VENTRAL HIPPOCAMPUS; ELEVATED X-MAZE; DIAZEPAM; IPSAPIRONE; F2692; RAT;
D O I
10.1007/BF02245882
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 (I 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.
引用
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页码:338 / 346
页数:9
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