EVIDENCE FOR POSTSYNAPTIC MEDIATION OF THE HYPOTHERMIC EFFECT OF 5-HT1A RECEPTOR ACTIVATION

被引:84
作者
OCONNELL, MT [1 ]
SARNA, GS [1 ]
CURZON, G [1 ]
机构
[1] INST NEUROL, DEPT NEUROCHEM, QUEEN SQ, LONDON WC1N 3BG, ENGLAND
关键词
FEEDING; 5-HT1A AGONISTS; 5-HT1A ANTAGONISTS; 5-HT BEHAVIOR; TEMPERATURE;
D O I
10.1111/j.1476-5381.1992.tb14382.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 The 5-HT1A ligand BMY 7378 (8-[2[4-(2-methoxyphenyl)-l-piperazinyl]ethyl]8-azaspirol [4,5]-decane-7,9-dione dihydrochloride, 0.032-2 mg kg-1, s.c.) caused hyperphagia, a response to the activation of presynaptic 5-HT1A receptors. 2 BMY 7378 (8 mg kg-1, s.c.) and the 5-HT1A agonist (8-hydroxy-2-(di-n-propylamino) tetralin(8-OH-DPAT), 0.10 and 0.25 mg kg-1 s.c.) also caused hypothermia. This was inhibited by (-)-pindolol (1 mg kg-1, i.p.) and not prevented by pretreatments with p-chlorophenylalanine which grossly depleted 5-hydroxytryptamine (5-HT) from terminal regions. The hypothermic effects are explicable by activation of postsynaptic 5-HT1A receptors. Infusion of BMY 7378 (8-64-mu-g) into the dorsal raphe was without convincing hypothermic effect. 3 BMY 7378 (8 mg kg-1, s.c.) inhibited another effect of activation of postsynaptic 5-HT1A receptors, i.e., the induction of components of the 5-HT syndrome by 8-OH-DPAT (0. 5, 1.0 mg kg-1, s.c.) which suggests that BMY 7378 has antagonistic as well as agonistic effects at these sites. 4 Partial agonist properties of BMY 7378 at postsynaptic sites were also indicated by doses for hypothermia being much greater than those for hyperphagia i.e., ED50 (hypothermia) > 2 mg kg-1, ED50 (hyperphagia) = 0.010 mg kg-1. This contrasts with the similar ED50 values for both the hypothermic (ED50=0.08-0.10 mg kg-1) and hyperphagic (ED50=0.06-0.10 mg kg-1) effects of 8-OH-DPAT. 5 The evidence obtained for mediation of the hypothermic response to 5-HT1A agonists by postsynaptic sites is relevant to the interpretation of the effects on it of antidepressant treatments and depressive illness.
引用
收藏
页码:603 / 609
页数:7
相关论文
共 49 条
[11]   PUTATIVE ANXIOLYTICS 8-OH-DPAT, BUSPIRONE AND TVX-Q-7821 ARE AGONISTS AT 5-HT1A AUTORECEPTORS IN THE RAPHE NUCLEI [J].
DOURISH, CT ;
HUTSON, PH ;
CURZON, G .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1986, 7 (06) :212-214
[12]   THE PHARMACOLOGY OF THE BEHAVIORAL AND HYPOTHERMIC RESPONSES OF RATS TO 8-HYDROXY-2-(DI-NORMAL-PROPYLAMINO)TETRALIN (8-OH-DPAT) [J].
GOODWIN, GM ;
DESOUZA, RJ ;
GREEN, AR ;
HEAL, DJ .
PSYCHOPHARMACOLOGY, 1987, 91 (04) :506-511
[13]   ATTENUATION BY ELECTROCONVULSIVE SHOCK AND ANTIDEPRESSANT DRUGS OF THE 5-HT1A RECEPTOR-MEDIATED HYPOTHERMIA AND SEROTONIN SYNDROME PRODUCED BY 8-OH-DPAT IN THE RAT [J].
GOODWIN, GM ;
DESOUZA, RJ ;
GREEN, AR .
PSYCHOPHARMACOLOGY, 1987, 91 (04) :500-505
[14]   THE PHARMACOLOGY OF THE HYPOTHERMIC RESPONSE IN MICE TO 8-HYDROXY-2-(DI-N-PROPYLAMINO)TETRALIN (8-OH-DPAT) - A MODEL OF PRESYNAPTIC 5-HT1 FUNCTION [J].
GOODWIN, GM ;
DESOUZA, RJ ;
GREEN, AR .
NEUROPHARMACOLOGY, 1985, 24 (12) :1187-1194
[15]   IDENTIFICATION OF PRE-SYNAPTIC SEROTONIN AUTORECEPTORS USING A NEW LIGAND - H-3-PAT [J].
GOZLAN, H ;
ELMESTIKAWY, S ;
PICHAT, L ;
GLOWINSKI, J ;
HAMON, M .
NATURE, 1983, 305 (5930) :140-142
[16]   SEX-RELATED DIFFERENCES IN CENTRAL ADRENERGIC-FUNCTION AND RESPONSIVENESS TO REPEATED ADMINISTRATION OF DESIPRAMINE OR ELECTROCONVULSIVE SHOCK [J].
HEAL, DJ ;
BRISTOW, LM ;
HURST, EM ;
ELLIOTT, JM ;
BUCKETT, WR .
BRITISH JOURNAL OF PHARMACOLOGY, 1989, 97 (01) :111-118
[17]   RAT-BRAIN SLICER - A SIMPLE DEVICE FOR RAPIDLY OBTAINING SERIAL SLABS OF FRESH BRAIN [J].
HENRY, JL ;
YASHPAL, K .
BRAIN RESEARCH BULLETIN, 1984, 13 (01) :195-197
[18]   BEHAVIORAL AND BIOCHEMICAL CONSEQUENCES FOLLOWING ACTIVATION OF 5HT1-LIKE AND GABA RECEPTORS IN THE DORSAL RAPHE NUCLEUS OF THE RAT [J].
HIGGINS, GA ;
BRADBURY, AJ ;
JONES, BJ ;
OAKLEY, NR .
NEUROPHARMACOLOGY, 1988, 27 (10) :993-1001
[19]   EFFECTS OF LOCAL APPLICATION OF 5-HT AND 8-OH-DPAT INTO THE DORSAL AND MEDIAN RAPHE NUCLEI ON MOTOR-ACTIVITY IN THE RAT [J].
HILLEGAART, V .
PHYSIOLOGY & BEHAVIOR, 1990, 48 (01) :143-148
[20]   EFFECTS OF LOCAL APPLICATION OF 5-HT AND 8-OH-DPAT INTO THE DORSAL AND MEDIAN RAPHE NUCLEI ON CORE TEMPERATURE IN THE RAT [J].
HILLEGAART, V .
PSYCHOPHARMACOLOGY, 1991, 103 (03) :291-296