A DOPAMINE DEFICIENCY MODEL OF LESCH-NYHAN DISEASE - THE NEONATAL-6-OHDA-LESIONED RAT

被引:59
作者
BREESE, GR
CRISWELL, HE
DUNCAN, GE
MUELLER, RA
机构
[1] Brain and Development Research Center, University of North Carolina School of Medicine, Chapel Hill
关键词
6-OHDA treatment; Adenosine receptors; Brain dopamine; D[!sub]1[!/sub]-dopamine receptors; D[!sub]1[!/sub]-receptor priming; Lesch-Nyhan syndrome; Neonatal; Self-mutilatory behavior;
D O I
10.1016/0361-9230(90)90240-Z
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Lesch-Nyhan syndrome is characterized by a deficiency of the enzyme hypoxanthine phosphoribosyl transferase (HPRT), compulsive self-mutilatory behavior (SMB), and a loss of central dopaminergic neurons. In order to model the loss of central dopamine-containing neurons in this developmental disorder, neonatal rat pups 3 days of age were given the neurotoxin 6-OHDA intracisternally to reduce brain dopamine. Accompanying the profound loss of dopamine produced by this treatment was an increase in striatal serotonin content. When these neonatally lesioned rats were challenged as adults with systemically administered L-DOPA or with muscimol administration into substantia nigra reticulata (SNR), SMB was observed, a response not observed in unlesioned rats. Thus, the neonatally lesioned rats exhibit increased susceptibility for SMB. Since a D1-dopamine antagonist blocked the SMB response to L-DOPA, it was proposed that D1-dopamine receptors were critical to this behavioral response. Basic investigations concerning D1-dopamine receptor mechanisms in the lesioned rats have been performed and these are reviewed. The data in the neonatally lesioned rats provide convincing evidence that the absence of central dopaminergic neurons is responsible for at least some of the neurological symptoms of the Lesch-Nyhan syndrome, a finding consistent with data collected in mice with an HPRT deficiency. © 1990.
引用
收藏
页码:477 / 484
页数:8
相关论文
共 57 条
  • [1] NEONATAL 6-HYDROXYDOPAMINE-INDUCED DOPAMINE DEPLETIONS - MOTOR-ACTIVITY AND PERFORMANCE IN MAZE-LEARNING
    ARCHER, T
    DANYSZ, W
    FREDRIKSSON, A
    JONSSON, G
    LUTHMAN, J
    SUNDSTROM, E
    TEILING, A
    [J]. PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1988, 31 (02) : 357 - 364
  • [2] D-1 DOPAMINE RECEPTOR CHANGES AFTER STRIATAL QUINOLINIC ACID LESION
    BARONE, P
    TUCCI, I
    PARASHOS, SA
    CHASE, TN
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1987, 138 (01) : 141 - 145
  • [3] SELF-INJURIOUS-BEHAVIOR IN RATS PRODUCED BY INTRANIGRAL MICROINJECTION OF GABA AGONISTS
    BAUMEISTER, AA
    FRYE, GD
    [J]. PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1984, 21 (01) : 89 - 95
  • [4] BITLER CM, 1986, J NEUROCHEM, V47, P107
  • [5] Breese G R, 1986, Adv Exp Med Biol, V204, P197
  • [6] BREESE GR, 1984, J PHARMACOL EXP THER, V231, P343
  • [7] BREESE GR, 1985, J PHARMACOL EXP THER, V235, P287
  • [8] SCH-23390 ANTAGONISM OF A D-2 DOPAMINE AGONIST DEPENDS UPON CATECHOLAMINERGIC NEURONS
    BREESE, GR
    MUELLER, RA
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1985, 113 (01) : 109 - 114
  • [9] BREESE GR, 1970, J PHARMACOL EXP THER, V174, P413
  • [10] NEONATAL-6-HYDROXYDOPAMINE TREATMENT - MODEL OF SUSCEPTIBILITY FOR SELF-MUTILATION IN THE LESCH-NYHAN SYNDROME
    BREESE, GR
    BAUMEISTER, AA
    MCCOWN, TJ
    EMERICK, SG
    FRYE, GD
    MUELLER, RA
    [J]. PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR, 1984, 21 (03) : 459 - 461