Dopaminergic brain system in the quaking mutant mouse.
Quaking mice (qk/qk), autosomal recessive mutants with central nervous system dysmyelinization, characterized behaviorally by abnormal locomotion and tremor, are found to have altered brain dopaminergic system parameters, in comparison with phenotypically normal heterozygous littermates. Dopamine metabolism is enhanced in structures of both nigrostriatal and mesolimbic systems, as revealed by increased metabolites content (that of homovanillic acid in striatum and concentration of 3,4-dihydroxy-phenylacetic acid in nucleus accumbens with tuberculum olfactorium) along with unchanged neurotransmitter levels in qk/qk mice. D1 and D2 receptor analysis via radioligand binding using [3H]-SCH 23390 and [3H]-spiperone, correspondingly, showed an increase of D2 receptor density with decreased affinity to D2 ligand in striatum of mutants: both Bmax and Kd were markedly higher. D1 and D2 receptor sensitivity in the quaking mouse was also altered. Stimulation of D1 receptors by a highly specific agonist SKF 38393 (2.5 and 5 mg/kg) decreased locomotor activity only in mutants, but not in controls. In contrast, qk/qk were less sensitive than phenotypically normal qk/+ mice to a selective D2 dopamine receptor agonist, LY 171555 (quinpirole, 1 and 2.5 mg/kg). The alterations found in the brain dopaminergic system of qk/qk mice may be responsible for the behavioral expression of this neurologic mutation.
Nikulina
E M
EM
Institute of Cytology and Genetics, Siberian Division of the Russian Academy of Sciences, Novosibirsk.
Skrinskaya
J A
JA
Avgustinovich
D F
DF
Popova
N K
NK
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004873:Ergolines / Q000494:pharmacology; D005260:Female; D006579:Heterozygote; D016014:Linear Models; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008821:Mice, Quaking; D009043:Motor Activity / Q000502:physiology*; D010641:Phenotype; D019257:Quinpirole; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D013268:Stimulation, Chemical
D004873:Ergolines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D001058:Apomorphine; D004298:Dopamine