Suppression of Serotonin Neuron Firing Increases Aggression in Mice

被引:81
作者
Audero, Enrica [1 ,3 ]
Mlinar, Boris [2 ]
Baccini, Gilda [2 ]
Skachokova, Zhiva K. [1 ]
Corradetti, Renato [2 ]
Gross, Cornelius [1 ]
机构
[1] European Mol Biol Lab, Mouse Biol Unit, I-00015 Monterotondo, Italy
[2] Univ Florence, Dept Preclin & Clin Pharmacol, I-50139 Florence, Italy
[3] Champalimaud Ctr Unknown, Champalimaud Neurosci Programme, P-1400038 Lisbon, Portugal
关键词
DORSAL RAPHE NUCLEUS; MONOAMINE-OXIDASE-A; 5-HT1A RECEPTOR AGONISTS; NORMAL ANXIETY-LIKE; RAT-BRAIN SLICES; SOCIAL INSTIGATION; GENE PROMOTER; BEHAVIOR; POLYMORPHISM; INHIBITION;
D O I
10.1523/JNEUROSCI.2067-12.2013
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Numerous studies link decreased serotonin metabolites with increased impulsive and aggressive traits. However, although pharmacological depletion of serotonin is associated with increased aggression, interventions aimed at directly decreasing serotonin neuron activity have supported the opposite association. Furthermore, it is not clear if altered serotonin activity during development may contribute to some of the observed associations. Here, we used two pharmacogenetic approaches in transgenic mice to selectively and reversibly reduce the firing of serotonin neurons in behaving animals. Conditional overexpression of the serotonin 1A receptor (Htr1a) in serotonin neurons showed that a chronic reduction in serotonin neuron firing was associated with heightened aggression. Overexpression of Htr1a in adulthood, but not during development, was sufficient to increase aggression. Rapid suppression of serotonin neuron firing by agonist treatment of mice expressing Htr1a exclusively in serotonin neurons also led to increased aggression. These data confirm a role of serotonin activity in setting thresholds for aggressive behavior and support a direct association between low levels of serotonin homeostasis and increased aggression.
引用
收藏
页码:8678 / 8688
页数:11
相关论文
共 51 条
  • [1] Neurochemical and anatomical identification of fast- and slow-firing neurones in the rat dorsal raphe nucleus using juxtacellular labelling methods in vivo
    Allers, KA
    Sharp, T
    [J]. NEUROSCIENCE, 2003, 122 (01) : 193 - 204
  • [2] Sporadic autonomic dysregulation and death associated with excessive serotonin autoinhibition
    Audero, Enrica
    Coppi, Elisabetta
    Mlinar, Boris
    Rossetti, Tiziana
    Caprioli, Antonio
    Al Banchaabouchi, Mumna
    Corradetti, Renato
    Gross, Cornelius
    [J]. SCIENCE, 2008, 321 (5885) : 130 - 133
  • [3] SUPPRESSION OF FIRING ACTIVITY OF 5-HT NEURONS IN THE DORSAL RAPHE BY ALPHA-ADRENOCEPTOR ANTAGONISTS
    BARABAN, JM
    AGHAJANIAN, GK
    [J]. NEUROPHARMACOLOGY, 1980, 19 (04) : 355 - 363
  • [4] The effects of tryptophan depletion and loading on laboratory aggression in men: time course and a food-restricted control
    Bjork, JM
    Dougherty, DM
    Moeller, FG
    Cherek, DR
    Swann, AC
    [J]. PSYCHOPHARMACOLOGY, 1999, 142 (01) : 24 - 30
  • [5] Heterogeneous Distribution of the Serotonin 5-HT1A Receptor mRNA in Chemically Identified Neurons of the Mouse Rostral Brainstem: Implications for the Role of Serotonin in the Regulation of Wakefulness and REM Sleep
    Bonnavion, Patricia
    Bernard, Jean-Francois
    Hamon, Michel
    Adrien, Joelle
    Fabre, Veronique
    [J]. JOURNAL OF COMPARATIVE NEUROLOGY, 2010, 518 (14) : 2744 - 2770
  • [6] BROWN GL, 1982, AM J PSYCHIAT, V139, P741
  • [7] ABNORMAL-BEHAVIOR ASSOCIATED WITH A POINT MUTATION IN THE STRUCTURAL GENE FOR MONOAMINE OXIDASE-A
    BRUNNER, HG
    NELEN, M
    BREAKEFIELD, XO
    ROPERS, HH
    VANOOST, BA
    [J]. SCIENCE, 1993, 262 (5133) : 578 - 580
  • [8] Development of violence in mice through repeated victory along with changes in prefrontal cortex neurochemistry
    Caramaschi, Doretta
    de Boer, Sietse F.
    de Vries, Han
    Koolhaas, Jaap M.
    [J]. BEHAVIOURAL BRAIN RESEARCH, 2008, 189 (02) : 263 - 272
  • [9] Differential role of the 5-HT1A receptor in aggressive and non-aggressive mice:: An across-strain comparison
    Caramaschi, Doretta
    de Boer, Sietse F.
    Koolhaas, Jaap M.
    [J]. PHYSIOLOGY & BEHAVIOR, 2007, 90 (04) : 590 - 601
  • [10] Role of genotype in the cycle of violence in maltreated children
    Caspi, A
    McClay, J
    Moffitt, TE
    Mill, J
    Martin, J
    Craig, IW
    Taylor, A
    Poulton, R
    [J]. SCIENCE, 2002, 297 (5582) : 851 - 854