Serotonin receptor 1A knockout: An animal model of anxiety-related disorder

被引:629
作者
Ramboz, S
Oosting, R
Amara, DA
Kung, HF
Blier, P
Mendelsohn, M
Mann, JJ
Brunner, D
Hen, R
机构
[1] Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA
[2] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA
[3] Solvay Pharmaceut, Weesp, Netherlands
[4] McGill Univ, Neurobiol Psychiat Unit, Montreal, PQ H3T 1E2, Canada
[5] New York State Psychiat Inst & Hosp, Dept Neurosci, New York, NY 10032 USA
[6] Columbia Univ, Dept Dev Psychobiol, New York, NY 10032 USA
[7] CUNY Hunter Coll, Dept Psychol, New York, NY 10021 USA
关键词
D O I
10.1073/pnas.95.24.14476
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
To investigate the contribution of individual serotonin (5-hydroxytryptamine; 5-HT) receptors to mood control, we have used homologous recombination to generate mice lacking specific serotonergic receptor subtypes. In the present report, we demonstrate that mice without 5-HT1A receptors display decreased exploratory activity and increased fear of aversive environments (open or elevated spaces). 5-HT1A knockout mice also exhibited a decreased immobility in the forced swim test, an effect commonly associated with antidepressant treatment. Although 5-HT1A receptors are involved in controlling the activity of serotonergic neurons, 5-HT1A knockout mice had normal levels of 5-HT and 5-hydroxyindoleacetic acid, possibly because of an up-regulation of 5-HT1B autoreceptors. Heterozygote 5-HT1A mutants expressed approximately one-half of wild-type receptor density and displayed intermediate phenotypes in most behavioral tests. These results demonstrate that 5-HT1A receptors are involved in the modulation of exploratory and fear-related behaviors and suggest that reductions in 5-HT1A receptor density due to genetic defects or environmental stressors might result in heightened anxiety.
引用
收藏
页码:14476 / 14481
页数:6
相关论文
共 34 条
  • [1] LOCALIZED ALTERATIONS IN PRESYNAPTIC AND POSTSYNAPTIC SEROTONIN BINDING-SITES IN THE VENTROLATERAL PREFRONTAL CORTEX OF SUICIDE VICTIMS
    ARANGO, V
    UNDERWOOD, MD
    GUBBI, AV
    MANN, JJ
    [J]. BRAIN RESEARCH, 1995, 688 (1-2) : 121 - 133
  • [2] ARTIGAS F, 1994, ARCH GEN PSYCHIAT, V51, P248
  • [3] DIFFERENTIAL RESPONSIVENESS OF THE RAT DORSAL AND MEDIAN RAPHE 5-HT SYSTEMS TO 5-HT1-RECEPTOR AGONISTS AND PARA-CHLOROAMPHETAMINE
    BLIER, P
    SERRANO, A
    SCATTON, B
    [J]. SYNAPSE, 1990, 5 (02) : 120 - 133
  • [4] CURRENT ADVANCES AND TRENDS IN THE TREATMENT OF DEPRESSION
    BLIER, P
    DEMONTIGNY, C
    [J]. TRENDS IN PHARMACOLOGICAL SCIENCES, 1994, 15 (07) : 220 - 226
  • [5] SEX-DIFFERENCES IN DEPRESSION - A ROLE FOR PREEXISTING ANXIETY
    BRESLAU, N
    SCHULTZ, L
    PETERSON, E
    [J]. PSYCHIATRY RESEARCH, 1995, 58 (01) : 1 - 12
  • [6] Insights into the neurobiology of impulsive behavior from serotonin receptor knockout mice
    Brunner, D
    Hen, R
    [J]. NEUROBIOLOGY OF SUICIDE: FROM THE BENCH TO THE CLINIC, 1997, 836 : 81 - 105
  • [7] REGULATION OF 5-HT RECEPTORS BY CORTICOSTEROIDS - WHERE DO WE STAND
    CHAOULOFF, F
    [J]. FUNDAMENTAL & CLINICAL PHARMACOLOGY, 1995, 9 (03) : 219 - 233
  • [8] DEVRY J, 1995, PSYCHOPHARMACOLOGY, V121, P1
  • [9] STRUGGLING AND FLUMAZENIL EFFECTS IN THE SWIMMING TEST ARE RELATED TO THE LEVEL OF ANXIETY IN MICE
    FERRE, P
    TERUEL, AF
    ESCORIHUELA, RM
    GARCIA, E
    ZAPATA, A
    TOBENA, A
    [J]. NEUROPSYCHOBIOLOGY, 1994, 29 (01) : 23 - 27
  • [10] File S.E., 1992, EXPT APPROACHES ANXI, P26