Modulation of the extracellular 5-hydroxytryptamine brain concentrations by the serotonin and noradrenaline reuptake inhibitor, milnacipran - Microdialysis studies in rats

被引:18
作者
Bel, N [1 ]
Artigas, F [1 ]
机构
[1] CSIC, Inst Invest Biomed Barcelona, IDIBAPS, Dept Neurochem, Barcelona 08036, Spain
关键词
5-HT uptake; 5-HT1A receptors; antidepressants; frontal cortex; hypothalamus; raphe; selective serotonin reuptake inhibitors;
D O I
10.1016/S0893-133X(99)00076-7
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
We examined the effects of the administration of milnacipran, a dual inhibitor of serotonin (5-hydroxy-tryptamine, 5-HT) and noradrenaline uptake on the 5-HT output in rat brain. Local milnacipran administration increased the 5-HT output in frontal cortex and the midbrain raphe nuclei 7- and 10-fold by a Ca2+- and tetrodotoxin-dependent mechanism. However, the subcutaneous administration of milnacipran (1-60 mg/kg SC) elevated the 5-HT output much less in these areas (200-230% of baseline at 60 mg/kg). In hypothalamus, 10 mg/kg SC raised 5-HT levels to 170%. The 5-HT1A antagonist WAY-100635 caused a small potentiation of the effects of milnacipran. The baseline 5-HT output was unaffected by 2-week treatments with milnacipran (30 and 60 mg/kg . day). The distinct regional profile and the lack of enhancement of its effects by WAY-100635 and prolonged treatment suggest that milnacipran does not exert its antidepressant action through an enhancement of the serotonergic function. [Neuropsychopharmacology 21:745-754,1999] (C) 1999 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.
引用
收藏
页码:745 / 754
页数:10
相关论文
共 48 条
[1]  
ADELL A, 1991, N-S ARCH PHARMACOL, V343, P237
[2]  
ADELL A, 1997, NEUROPHARMACOLOGY, V36, P745
[3]   Acceleration of the effect of selected antidepressant drugs in major depression by 5-HT1A antagonists [J].
Artigas, F ;
Romero, L ;
deMontigny, C ;
Blier, P .
TRENDS IN NEUROSCIENCES, 1996, 19 (09) :378-383
[4]   SELECTIVE SEROTONIN NORADRENALINE REUPTAKE INHIBITORS (SNRIS) - PHARMACOLOGY AND THERAPEUTIC POTENTIAL IN THE TREATMENT OF DEPRESSIVE-DISORDERS [J].
ARTIGAS, F .
CNS DRUGS, 1995, 4 (02) :79-89
[5]   EXTRACELLULAR SEROTONIN AND 5-HYDROXYINDOLEACETIC ACID IN HYPOTHALAMUS OF THE UNANESTHETIZED RAT MEASURED BY INVIVO DIALYSIS COUPLED TO HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY WITH ELECTROCHEMICAL DETECTION - DIALYSATE SEROTONIN REFLECTS NEURONAL RELEASE [J].
AUERBACH, SB ;
MINZENBERG, MJ ;
WILKINSON, LO .
BRAIN RESEARCH, 1989, 499 (02) :281-290
[6]   SUPPRESSION OF FIRING ACTIVITY OF 5-HT NEURONS IN THE DORSAL RAPHE BY ALPHA-ADRENOCEPTOR ANTAGONISTS [J].
BARABAN, JM ;
AGHAJANIAN, GK .
NEUROPHARMACOLOGY, 1980, 19 (04) :355-363
[7]  
Bel N, 1996, J PHARMACOL EXP THER, V278, P1064
[8]   FLUVOXAMINE PREFERENTIALLY INCREASES EXTRACELLULAR 5-HYDROXYTRYPTAMINE IN THE RAPHE NUCLEI - AN INVIVO MICRODIALYSIS STUDY [J].
BEL, N ;
ARTIGAS, F .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1992, 229 (01) :101-103
[9]   CHRONIC TREATMENT WITH FLUVOXAMINE INCREASES EXTRACELLULAR SEROTONIN IN FRONTAL-CORTEX BUT NOT IN RAPHE NUCLEI [J].
BEL, N ;
ARTIGAS, F .
SYNAPSE, 1993, 15 (03) :243-245
[10]   CURRENT ADVANCES AND TRENDS IN THE TREATMENT OF DEPRESSION [J].
BLIER, P ;
DEMONTIGNY, C .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1994, 15 (07) :220-226