Journal
NEUROSCIENCE
Volume 142, Issue 4, Pages 1245-1253Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2006.07.005
Keywords
sensorimotor function; Parkinson's disease; amphetamine; apomorphine; L-DOPA
Categories
Funding
- NIA NIH HHS [P01 AG022074, AG18440, AG022074, R01 AG018440, R37 AG018440] Funding Source: Medline
- NIEHS NIH HHS [U54 ES012078, U54 ES012078-01, U54ES12078] Funding Source: Medline
- NINDS NIH HHS [T32 NS07449-05, P50 NS038367, P50NS38367, T32 NS007449, P50 NS038367-02] Funding Source: Medline
Ask authors/readers for more resources
Overexpression of alpha-synuclein causes familial Parkinson's disease and abnormal aggregates of the protein are present in sporadic cases of the disease. We have examined the behavioral effects of direct and indirect dopaminergic agonists in transgenic mice expressing human alpha-synuclein under the Thy-1 promoter (Thy1-aSyn, alpha-synuclein overexpressor), which exhibit progressive impairments in behavioral tests sensitive to nigrostriatal dopamine dysfunction. Male Thy1-aSyn and wild-type mice received vehicle, benserazide/L-DOPA (25 mg/kg, i.p.), high (2 mg/kg, s.c.) and low doses (0.125, 0.25, 0.5 mg/kg, s.c.) of apomorphine, and amphetamine (5 mg/kg, i.p.), beginning at 3 months of age, and were tested on the challenging beam, spontaneous activity, pole test, and gait. L-DOPA had a paradoxical effect and worsened the deficits in Thy1-aSyn mice compared with controls, whereas the high dose of apomorphine only produced few deficits above those already present in Thy1-aSyn. In contrast to wild-type mice, Thy1-aSyn mice did not show amphetamine-induced stereotypies. The results indicate that chronic overexpression of alpha-synuclein led to abnormal pharmacological responses in mice. (c) 2006 Published by Elsevier Ltd on behalf of IRBO.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available