NEURONAL CIRCUITS INVOLVED IN THE ANXIOLYTIC EFFECTS OF THE 5-HT1A RECEPTOR AGONISTS 8-OH-DPAT, IPSAPIRONE AND BUSPIRONE IN THE RAT

被引:132
作者
SCHREIBER, R [1 ]
DEVRY, J [1 ]
机构
[1] TROPONWERKE GMBH & CO KG,INST NEUROBIOL,DEPT PSYCHOPHARMACOL,D-51063 COLOGNE,GERMANY
关键词
ANXIOLYSIS; DORSAL RAPHE NUCLEUS; HIPPOCAMPUS; 5-HT1A RECEPTOR LIGAND (RAT); ULTRASONIC VOCALIZATION;
D O I
10.1016/0014-2999(93)90531-L
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In rats, the 5-HT1A receptor full agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the 5-HT1A receptor partial agonists ipsapirone and buspirone dose dependently and completely inhibited shock-induced ultrasonic vocalization after systemic injection and after microinjection into the dorsal raphe nucleus, a brain region rich in somatodendritic 5-HT1A receptors. As compared with injection into the dorsal raphe nucleus, ipsapirone and 8-OH-DPAT were significantly less potent after microinjection into the lateral ventricle or the median raphe nucleus. Depletion of brain 5-HT (5-hydroxytryptamine) by means of 5,7-dihydroxytryptamine or parachlorophenylalanine inhibited ultrasonic vocalization. In lesioned rats, however, ipsapirone (i.p. or dorsal raphe nucleus) and 8-OH-DPAT (dorsal raphe nucleus) retained their ability to inhibit ultrasonic vocalization and, in nonlesioned rats, bilateral injection of ipsapirone, buspirone and 8-OH-DPAT into the dorsal hippocampus and the amygdala - two brain regions rich in postsynaptic 5-HT1A receptors - also inhibited ultrasonic vocalization. In a Geller-Seifter conflict test, i.p. and local injection of 8-OH-DPAT in the dorsal raphe nucleus and the hippocampus selectively enhanced punished responding. It is suggested that both presynaptic and (possibly to a lesser extent) postsynaptic 5-HT1A receptors are involved in the anxiolytic effects of ipsapirone, buspirone, and 8-OH-DPAT.
引用
收藏
页码:341 / 351
页数:11
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