Action of harman (1-methyl-beta-carboline) on the brain: Body temperature and in vivo efflux of 5-HT from hippocampus of the rat

被引:61
作者
Adell, A
Biggs, TA
Myers, RD
机构
[1] E CAROLINA UNIV,SCH MED,DEPT PHARMACOL,GREENVILLE,NC 27858
[2] E CAROLINA UNIV,SCH MED,DEPT PSYCHIAT MED,GREENVILLE,NC 27858
[3] CSIC,CID,DEPT NEUROCHEM,ES-08034 BARCELONA,SPAIN
关键词
harman (1-methyl-beta-carboline); body temperature; serotonin; (+/-)-pindolol; p-chlorophenylalanine; hippocampus; microdialysis;
D O I
10.1016/S0028-3908(96)00043-3
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Harman (1-methyl-beta-carboline) has been shown previously to act on the hippocampus of the rat in terms of its evocation of anxiogenic responses and induction of alcohol preference. In the present experiments, the localized perfusion of 200 mu M harman in the dorsal hippocampus of freely moving rats increased the levels of serotonin (5-HT) but not 5-hydroxyindoleacetic acid (5-HIAA) in cerebral dialysates. The systemic administration of 5.0-20 mg/kg harman also enhanced 5-HT in the perfusates but reduced the levels of 5-HIAA in a dose-dependent manner, probably as a result of the inhibition of the enzyme monoamine oxidase type A (MAO-A). Harman given systemically in doses of 2.5-20 mg/kg induced an intense hypothermia, with a maximum fall produced by the 5.0 mg/kg dose. This fall in body temperature (T-b) induced by 5.0 mg/kg barman was not antagonized by 5.0 mg/kg of (+/-)-pindolol. Further, pretreatment of the rats with parachlorophenylalanine (pCPA) also failed to alter the barman-induced hypothermia. The systemic administration of 10 mg/kg of the MAO-A inhibitor, clorgyline, also lowered T-b significantly. Overall, the present experiments show that harman apparently influences 5-HT systems in the brain by its action in inhibiting MAO-A. This property is likely responsible also for the harman-induced increase of 5-HT in the hippocampus of the rats. Copyright (C) 1996 Elsevier Science Ltd.
引用
收藏
页码:1101 / 1107
页数:7
相关论文
共 40 条
[1]   HYPOTHERMIC EFFECT OF HARMALA ALKALOID IN RATS - INVOLVEMENT OF SEROTONERGIC MECHANISM [J].
ABDELFATTAH, AFM ;
MATSUMOTO, K ;
GAMMAZ, HAK ;
WATANABE, H .
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1995, 52 (02) :421-426
[2]   INCREASED ALCOHOL INTAKE IN LOW ALCOHOL-DRINKING RATS AFTER CHRONIC INFUSION OF THE BETA-CARBOLINE HARMAN INTO THE HIPPOCAMPUS [J].
ADELL, A ;
MYERS, RD .
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1994, 49 (04) :949-953
[3]   5-HT, DOPAMINE, NOREPINEPHRINE, AND RELATED METABOLITES IN BRAIN OF LOW ALCOHOL-DRINKING (LAD) RATS SHIFT AFTER CHRONIC INTRAHIPPOCAMPAL INFUSION OF HARMAN [J].
ADELL, A ;
MYERS, RD .
NEUROCHEMICAL RESEARCH, 1995, 20 (02) :209-215
[4]  
ADELL A, 1991, N-S ARCH PHARMACOL, V343, P237
[5]   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
[6]   TREMORIGENIC EFFECT AND INHIBITION OF TRYPTAMINE AND SEROTONIN RECEPTOR-BINDING BY BETA-CARBOLINES [J].
AIRAKSINEN, MM ;
LECKLIN, A ;
SAANO, V ;
TUOMISTO, L ;
GYNTHER, J .
PHARMACOLOGY & TOXICOLOGY, 1987, 60 (01) :5-8
[7]  
BEL N, 1995, N-S ARCH PHARMACOL, V351, P475
[8]  
BOSIN TR, 1989, ALCOHOL, V5, P505
[9]   HIGH-AFFINITY (TRYPTAMINE-H-3 BINDING-SITES IN VARIOUS ORGANS OF THE RAT [J].
BRUNING, G ;
ROMMELSPACHER, H .
LIFE SCIENCES, 1984, 34 (15) :1441-1446
[10]   INHIBITION BY BETA-CARBOLINES OF MONOAMINE UPTAKE INTO A SYNAPTOSOMAL PREPARATION - STRUCTURE-ACTIVITY-RELATIONSHIPS [J].
BUCKHOLTZ, NS ;
BOGGAN, WO .
LIFE SCIENCES, 1977, 20 (12) :2093-2099