METHYLENEDIOXYMETHAMPHETAMINE INDUCES SPONTANEOUS TAIL-FLICKS IN THE RAT VIA 5-HT1A RECEPTORS

被引:15
作者
MILLAN, MJ
COLPAERT, FC
机构
[1] Neurobiology Division, Fondax-Groupe de Recherche Servier, 92800 Puteaux
关键词
MDMA (3,4-METHYLENEDIOXYMETHAMPHETAMINE); 5-HT; (5-HYDROXYTRYPTAMINE; SEROTONIN); 5-HT1A RECEPTORS; BMY; 7378; NAN-190;
D O I
10.1016/0014-2999(91)90029-P
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In rats lightly restrained in horizontal cylinders, (+/-)-3,4-methylenedioxymethamphetamine (MDMA) dose dependently (0.16-10.0 mg/kg, s.c.) elicited spontaneous tail-flicks; that is, tail-flicks in the absence of extraneous stimulation. In contrast, amphetamine over a similar dose-range was inactive. Selective inhibitors of 5-hydroxytryptamine (5-HT) uptake and carrier-mediated 5-HT release, paroxetine and citalpram, did not induce spontaneous tail-flicks themselves and blocked those induced by MDMA. In distinction, maprotiline and bupropion, selective inhibitors of noradrenaline and dopamine uptake, respectively, failed to modify the action of MDMA. Spontaneous tail-flicks elicited by MDMA were unaffected by the selective 5-HT3 receptor antagonists, ICS 205,930 and GR 38032F. They were attenuated by the mixed 5-HT1/5-HT2 receptor antagonist, methiotepin, the mixed 5-HT1A/5-HT1B receptor antagonist, (-)-alprenolol and the mixed 5-HT1A/5-HT2 receptor antagonist, spiperone, but not by the selective 5-HT1C/5-HT2 receptor antagonists, ritanserin, ICI 169,369 and ketanserin. The novel 5-HT1A receptor antagonists, BMY 7378 and NAN-190, each abolished MDMA-evoked spontaneous tail-flicks. Selective D1, D2, alpha-1, alpha-2, beta-1 and beta-2 antagonists had little influence upon induction of spontaneous tail-flicks by MDMA. These data indicate that MDMA evokes spontaneous tail-flicks in the rat via a release of 5-HT which acts at 5-HT1A receptors. Thus, 5-HT1A receptors appear to be involved in the acute functional actions of MDMA.
引用
收藏
页码:145 / 152
页数:8
相关论文
共 49 条
[1]   AN INVIVO DIALYSIS AND BEHAVIORAL-STUDY OF THE RELEASE OF 5-HT BY PARA-CHLOROAMPHETAMINE IN RESERPINE-TREATED RATS [J].
ADELL, A ;
SARNA, GS ;
HUTSON, PH ;
CURZON, G .
BRITISH JOURNAL OF PHARMACOLOGY, 1989, 97 (01) :206-212
[2]  
ARNT J, 1987, DOPAMINE RECEPTORS, P199
[3]  
BARBACCIA ML, 1986, J PHARMACOL EXP THER, V236, P307
[4]   PHARMACOLOGIC PROFILE OF MDMA (3,4-METHYLENEDIOXYMETHAMPHETAMINE) AT VARIOUS BRAIN RECOGNITION SITES [J].
BATTAGLIA, G ;
BROOKS, BP ;
KULSAKDINUN, C ;
DESOUZA, EB .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1988, 149 (1-2) :159-163
[5]   MDMA-INDUCED NEUROTOXICITY - PARAMETERS OF DEGENERATION AND RECOVERY OF BRAIN-SEROTONIN NEURONS [J].
BATTAGLIA, G ;
YEH, SY ;
DESOUZA, EB .
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1988, 29 (02) :269-274
[6]   INVITRO STUDIES WITH ICI-169,369, A CHEMICALLY NOVEL 5-HT ANTAGONIST [J].
BLACKBURN, TP ;
THORNBER, CW ;
PEARCE, RJ ;
COX, B .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1988, 150 (03) :247-256
[7]   PHARMACOLOGICAL PROPERTIES OF GR38032F, A NOVEL ANTAGONIST AT 5-HT3 RECEPTORS [J].
BUTLER, A ;
HILL, JM ;
IRELAND, SJ ;
JORDAN, CC ;
TYERS, MB .
BRITISH JOURNAL OF PHARMACOLOGY, 1988, 94 (02) :397-412
[8]   CENTRAL SEROTONIN RECEPTORS - EFFECTOR SYSTEMS, PHYSIOLOGICAL ROLES AND REGULATION [J].
CONN, PJ ;
SANDERSBUSH, E .
PSYCHOPHARMACOLOGY, 1987, 92 (03) :267-277
[9]  
CONN PJ, 1987, J PHARMACOL EXP THER, V242, P552
[10]  
COOPER BR, 1980, J PHARMACOL EXP THER, V215, P2127