caa a22 4500 469118458 CHVBK 20180323133131.0 cr unu---uuuuu 170328e19921101xx s 000 0 eng 10.1007/BF02245882 doi (NATIONALLICENCE)springer-10.1007/BF02245882 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 [Elektronische Daten] [Ian Wright, N. Upton, C. Marsden] 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. Springer-Verlag, 1992 Microdialysis nationallicence 5-HT nationallicence Ventral hippocampus nationallicence Elevated X-maze nationallicence Diazepam nationallicence Ipsapirone nationallicence F2692 nationallicence Rat nationallicence Wright Ian Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, NG7 2UH, Nottingham, UK aut Upton N. SmithKline Beecham, Medicinal Research Centre, Coldharbour Road, CM19 5AD, Harlow, Essex, UK aut Marsden C. Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, NG7 2UH, Nottingham, UK aut Psychopharmacology Springer-Verlag 109/3(1992-11-01), 338-346 0033-3158 109:3<338 1992 109 213 https://doi.org/10.1007/BF02245882 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02245882 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wright Ian Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, NG7 2UH, Nottingham, UK aut NATIONALLICENCE 700 1- Upton N. SmithKline Beecham, Medicinal Research Centre, Coldharbour Road, CM19 5AD, Harlow, Essex, UK aut NATIONALLICENCE 700 1- Marsden C. Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, NG7 2UH, Nottingham, UK aut NATIONALLICENCE 773 0- Psychopharmacology Springer-Verlag 109/3(1992-11-01), 338-346 0033-3158 109:3<338 1992 109 213 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer