Locus coeruleus neuronal activity and noradrenaline availability in the frontal cortex of rats chronically treated with imipramine effect of α2-adrenoceptor blockade

被引:45
作者
Linnér, L
Arborelius, L
Nomikos, GG
Bertilsson, L
Svensson, TH [1 ]
机构
[1] Karolinska Inst, Dept Physiol & Pharmacol, Sect Neuropsychopharmacol, S-17177 Stockholm, Sweden
[2] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA
[3] Eli Lilly & Co, Lilly Corp Ctr, Neurosci Res, Indianapolis, IN 46285 USA
[4] Huddinge Univ Hosp, Karolinska Inst, Dept Med Lab Sci & Technol, Div Clin Pharmacol, S-14186 Huddinge, Sweden
关键词
noradrenaline; tricyclic antidepressants; alpha(2)-adrenoceptors; electrophysiology; microdialysis;
D O I
10.1016/S0006-3223(99)00126-2
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: previous studies indicate a reduced feed-back inhibition of brain noradrenaline (NA) neurons in the locus coeruleus (LC) during chronic administration of antidepressants which inhibit the NA reuptake mechanism due to functional downregulation of somatodendritic alpha(2)-adrenoceptors in the LC. Therefore, we have here studied the LC neuronal responsiveness to administration of the alpha(2)-adpenoceptor antagonist idazoxan (IDA) after both short-term and long-term imipramine (IMI) administration. Methods: Rats were treated for different periods with systemic IMI. In these rats, basal activity of central noradrenergic function and the effect of IDA was assessed by means of extracellular single-cell recording from LC neurons and in vivo microdialysis of extracellular NA levels in the frontal cortex (FC), Results: The average firing rate of LC neurons was significantly reduced in rats by short-term IMI treatment compared with long-term treatment. The output of NA in the FC of all IMI-treated animals was significantly increased compared with saline-treated rats. Moreover, the enhancing effect of IDA on both the firing rate of LC neurons and the cortical NA output was larger in rats after long-term treatment with IMI than after shout-term administration. Conclusions: Our results clearly support the nation of development of functional downregulation of alpha(2)-autoreceptors on LC neurons during chronic administration of NA reuptake inhibiting antidepressants. Moreover, the data suggest that addition of alpha(2)-adrenoceptor antagonists may augment the clinical effect of such drugs in major depression. (C) 1999 Society of Biological Psychiatry.
引用
收藏
页码:766 / 774
页数:9
相关论文
共 34 条
[1]  
ABERCROMBIE ED, 1991, MICRODIALYSIS NEUROS, P253
[2]  
ARBORELIUS L, 1995, N-S ARCH PHARMACOL, V352, P157
[3]   The 5-HT1A receptor antagonist (S)-UH-301 augments the increase in extracellular concentrations of 5-HT in the frontal cortex produced by both acute and chronic treatment with citalopram [J].
Arborelius, L ;
Nomikos, GG ;
Hertel, P ;
Salmi, P ;
Grillner, P ;
Hook, BB ;
Hacksell, U ;
Svensson, TH .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 1996, 353 (06) :630-640
[4]  
ARTIGAS F, 1994, ARCH GEN PSYCHIAT, V51, P248
[5]   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
[6]  
BLIER P, 1983, J NEUROSCI, V3, P1270
[7]   STRESS, ANTIDEPRESSANT DRUGS, AND THE LOCUS-COERULEUS [J].
BRADY, LS .
BRAIN RESEARCH BULLETIN, 1994, 35 (5-6) :545-556
[8]   STEADY-STATE CONCENTRATIONS OF IMIPRAMINE AND ITS METABOLITES IN RELATION TO THE SPARTEINE DEBRISOQUINE POLYMORPHISM [J].
BROSEN, K ;
KLYSNER, R ;
GRAM, LF ;
OTTON, SV ;
BECH, P ;
BERTILSSON, L .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1986, 30 (06) :679-684
[9]   Effects of desipramine and maprotiline on the coeruleus-cortical noradrenergic system in anaesthetized rats [J].
Ceci, A ;
Borsini, F .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1996, 312 (02) :189-193
[10]   EFFECTS OF A SELECTIVE 5-HT REUPTAKE BLOCKER, CITALOPRAM, ON THE SENSITIVITY OF 5-HT AUTORECEPTORS - ELECTROPHYSIOLOGICAL STUDIES IN THE RAT-BRAIN [J].
CHAPUT, Y ;
DEMONTIGNY, C ;
BLIER, P .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 1986, 333 (04) :342-348