Mineralocorticoid receptors in the ventral tegmental area regulate dopamine efflux in the basolateral amygdala during the expression of conditioned fear

被引:13
作者
de Oliveira, Amanda R. [1 ,2 ]
Reimer, Adriano E. [1 ,2 ]
Brandao, Marcus L. [1 ,2 ]
机构
[1] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Lab Psicobiol, BR-14090901 Ribeirao Preto, SP, Brazil
[2] Inst Neurociencias & Comportamento INeC, Ribeirao Preto, SP, Brazil
基金
巴西圣保罗研究基金会;
关键词
Fear conditioning; Mineralocorticoid receptors; Glucocorticoid receptors; Ventral tegmental area; Basolateral amygdala complex; Dopamine; ELEVATED PLUS-MAZE; RAT-BRAIN; GLUCOCORTICOID-RECEPTORS; CORTICOSTEROID RECEPTOR; LIMBIC STRUCTURES; STRESS HORMONES; MECHANISMS; MODULATE; ANXIETY; NEURONS;
D O I
10.1016/j.psyneuen.2014.02.010
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Despite the recognized involvement of corticosteroids in the modulation of emotional behavior, the specific role of mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) in the expression of conditioned fear responses is still open to investigation. The present study sought to clarify the involvement of both types of corticosteroid receptors in two different brain regions the ventral tegmental area (VTA) and the basolateral amygdala complex (BLA) on the expression of conditioned fear. The first experiment assessed the effects of intra-VTA or intra-BLA administration of spironolactone (MR antagonist) or mifepristone (GR antagonist) on the expression of conditioned freezing to a light-CS and on motor perfo rmance in the open-field test. Intra-VTAspironolactone, but not mifepristone, attenuated the expression of the conditioned freezing response whereas intra-BLA spironolactone or mifepristone had no significant effects. These treatments did not affect motor performance in the open-field test. Since dopamine is released in the BLA from the VTA during the expression of conditioned fear, the anxiolytic-like effect of decreased corticosteroid activity in the fi rst experiment could be associated with changes in dopaminergic neurotransmission. The second experiment, using in vivo microdialysis, investigated the role of MRs in the VTA on dopamine levels in the BLA during the expression of conditioned fear. Blocking MRs loca lly in the VTAwith spironolactone reduced dopamine efflux in the BLA and decreased the expression of conditioned freezing in response to the CS. Taken together, the data indicate that corticosterone, acting locally on MRs in the VTA, stimulates dopamine efflux in the BLA, which facilitates the expression of conditioned freezing to a light-CS. (C) 2014 Elsevier Ltd. All rights reserved.
引用
收藏
页码:114 / 125
页数:12
相关论文
共 52 条
[21]   Aripiprazole: A clinical review of its use for the treatment of anxiety disorders and anxiety as a comorbidity in mental illness [J].
Katzman, Martin A. .
JOURNAL OF AFFECTIVE DISORDERS, 2011, 128 :S11-S20
[22]   ANXIOLYTIC-LIKE EFFECTS OF SELECTIVE MINERALOCORTICOID AND GLUCOCORTICOID ANTAGONISTS ON FEAR-ENHANCED BEHAVIOR IN THE ELEVATED PLUS-MAZE [J].
KORTE, SM ;
DEBOER, SF ;
DEKLOET, ER ;
BOHUS, B .
PSYCHONEUROENDOCRINOLOGY, 1995, 20 (04) :385-394
[23]   The emotional brain, fear, and the amygdala [J].
LeDoux, J .
CELLULAR AND MOLECULAR NEUROBIOLOGY, 2003, 23 (4-5) :727-738
[24]   International Union of Pharmacology. LXV. The pharmacology and classification of the nuclear receptor superfamily: Glucocorticoid, mineralocorticoid, progesterone, and androgen receptors [J].
Lu, Nick Z. ;
Wardell, Suzanne E. ;
Burnstein, Kerry L. ;
Defranco, Donald ;
Fuller, Peter J. ;
Giguere, Vincent ;
Hochberg, Richard B. ;
McKay, Lorraine ;
Renoir, Jack-Michel ;
Weigel, Nancy L. ;
Wilson, Elizabeth M. ;
McDonnell, Donald P. ;
Cidlowski, John A. .
PHARMACOLOGICAL REVIEWS, 2006, 58 (04) :782-797
[25]   The acute effects of corticosteroids on cognition: Integration of animal and human model studies [J].
Lupien, SJ ;
McEwen, BS .
BRAIN RESEARCH REVIEWS, 1997, 24 (01) :1-27
[26]   The amygdala and fear conditioning: Has the nut been cracked? [J].
Maren, S ;
Fanselow, MS .
NEURON, 1996, 16 (02) :237-240
[27]   Metyrapone Administration Reduces the Strength of an Emotional Memory Trace in a Long-Lasting Manner [J].
Marin, Marie-France ;
Hupbach, Almut ;
Maheu, Francoise S. ;
Nader, Karim ;
Lupien, Sonia J. .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2011, 96 (08) :E1221-E1227
[28]   Involvement of dopaminergic mechanisms in the nucleus accumbens core and shell subregions in the expression of fear conditioning [J].
Martinez, R. C. R. ;
Oliveira, A. R. ;
Macedo, C. E. ;
Molina, V. A. ;
Brandao, M. L. .
NEUROSCIENCE LETTERS, 2008, 446 (2-3) :112-116
[29]   UPTAKE OF CORTICOSTERONE BY RAT BRAIN AND ITS CONCENTRATION BY CERTAIN LIMBIC STRUCTURES [J].
MCEWEN, BS ;
WEISS, JM ;
SCHWARTZ, LS .
BRAIN RESEARCH, 1969, 16 (01) :227-+
[30]   Spironolactone and low-dose dexamethasone enhance extinction of contextual fear conditioning [J].
Ninomiya, Ester Mayumi ;
Martynhak, Bruno Jacson ;
Zanoveli, Janaina M. ;
Correia, Diego ;
da Cunha, Claudio ;
Andreatini, Roberto .
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, 2010, 34 (07) :1229-1235