Dopamine deficiency in the weaver mutant mouse - PubMed (original) (raw)
Dopamine deficiency in the weaver mutant mouse
M J Schmidt et al. J Neurosci. 1982 Mar.
Abstract
The dopamine system in weaver mutant mice (B6CBA-Aw-J/A background) was studied. Dopamine was 27% lower in the olfactory tubercle, 77% lower in the frontal cortex, and 75% lower in the striatum of 6-month-old weaver mice compared to control mice of the same age. Norepinephrine and serotonin were not lower in these brain areas. Tyrosine hydroxylase activity in the striatum was measured with a radiometric assay and was 70% lower in weaver mice. Examination of mice from 11 to 180 days of age revealed that the dopamine system failed to develop in weaver mice. Motor activity in individual animals was assessed using circular photocell activity cages with minimal illumination. Apomorphine and pergolide, direct dopamine agonists, increased activity more in weaver mice than in normal littermates. Amphetamine, which releases endogenous stores of dopamine, was less active in mutant mice. These findings provide suggestive evidence that postsynaptic dopamine receptors in weaver mutants might have become supersensitive as a result of lower levels of dopamine in motor areas of the brain. Anatomical evidence of dopamine system abnormalities was found in weaver mice by examination of serial sections cut from the midbrain of mutant and normal mice. The pars compacta of the substantia nigra in weaver mice appeared hypocellular when compared with the corresponding sections from controls. Fewer large neurons were seen in the affected animals. This study illustrates that weaver mice have specific deficiencies in the dopamine system. The weaver mouse might provide a way of examining the biochemical and behavioral effects of long term dopamine deficiency and a way to examine drugs to treat dopamine-deficient states in vivo.
Similar articles
- Serotonin content is elevated in the dopamine deficient striatum of the weaver mutant mouse.
Stotz EH, Triarhou LC, Ghetti B, Simon JR. Stotz EH, et al. Brain Res. 1993 Mar 26;606(2):267-72. doi: 10.1016/0006-8993(93)90994-x. Brain Res. 1993. PMID: 8490719 - Expression of the weaver gene in dopamine-containing neural systems is dose-dependent and affects both striatal and nonstriatal regions.
Roffler-Tarlov S, Graybiel AM. Roffler-Tarlov S, et al. J Neurosci. 1986 Nov;6(11):3319-30. doi: 10.1523/JNEUROSCI.06-11-03319.1986. J Neurosci. 1986. PMID: 3772434 Free PMC article. - Patterns of cell and fiber vulnerability in the mesostriatal system of the mutant mouse weaver. I. Gradients and compartments.
Graybiel AM, Ohta K, Roffler-Tarlov S. Graybiel AM, et al. J Neurosci. 1990 Mar;10(3):720-33. doi: 10.1523/JNEUROSCI.10-03-00720.1990. J Neurosci. 1990. PMID: 1690789 Free PMC article. - Differential effect of dopamine deficiency on the expression of NMDA receptor subunits in the weaver mouse brain.
Fragioudaki K, Kouvelas ED, Mitsacos A. Fragioudaki K, et al. Eur J Neurosci. 2003 May;17(10):2056-64. doi: 10.1046/j.1460-9568.2003.02650.x. Eur J Neurosci. 2003. PMID: 12786972
Cited by
- GIRK Channels as Candidate Targets for the Treatment of Substance Use Disorders.
Kotajima-Murakami H, Ide S, Ikeda K. Kotajima-Murakami H, et al. Biomedicines. 2022 Oct 13;10(10):2552. doi: 10.3390/biomedicines10102552. Biomedicines. 2022. PMID: 36289814 Free PMC article. Review. - The weaver mutation of GIRK2 results in a loss of inwardly rectifying K+ current in cerebellar granule cells.
Surmeier DJ, Mermelstein PG, Goldowitz D. Surmeier DJ, et al. Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):11191-5. doi: 10.1073/pnas.93.20.11191. Proc Natl Acad Sci U S A. 1996. PMID: 8855331 Free PMC article. - Age-related changes in striatal dopamine D2 receptor binding in weaver mice and effects of ventral mesencephalic grafts.
Kaseda Y, Ghetti B, Low WC, Norton J, Brittain H, Triarhou LC, Richter JA, Simon JR. Kaseda Y, et al. Exp Brain Res. 1990;83(1):1-8. doi: 10.1007/BF00232187. Exp Brain Res. 1990. PMID: 2150046 - Intrastriatal implants of mesencephalic cell suspensions in weaver mutant mice: ultrastructural relationships of dopaminergic dendrites and axons issued from the graft.
Triarhou LC, Brundin P, Doucet G, Norton J, Björklund A, Ghetti B. Triarhou LC, et al. Exp Brain Res. 1990;79(1):3-17. doi: 10.1007/BF00228869. Exp Brain Res. 1990. PMID: 1968850 - The weaver mouse gain-of-function phenotype of dopaminergic midbrain neurons is determined by coactivation of wvGirk2 and K-ATP channels.
Liss B, Neu A, Roeper J. Liss B, et al. J Neurosci. 1999 Oct 15;19(20):8839-48. doi: 10.1523/JNEUROSCI.19-20-08839.1999. J Neurosci. 1999. PMID: 10516303 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous