Behavioral and immunohistochemical effects of chronic intravenous and subcutaneous infusions of varying doses of rotenone
1. Exp Neurol. 2004 Jun;187(2):418-29. doi: 10.1016/j.expneurol.2004.01.023.
Behavioral and immunohistochemical effects of chronic intravenous and
subcutaneous infusions of varying doses of rotenone.
Fleming SM(1), Zhu C, Fernagut PO, Mehta A, DiCarlo CD, Seaman RL, Chesselet MF.
Author information:
(1)Department of Neurology, The David Geffen School of Medicine at UCLA, Los
Angeles, CA 90095-1769, USA.
Mitochondrial toxins such as the complex 1 inhibitor rotenone are widely used as
pesticides and may be present in military environments. Administration of
rotenone can induce biochemical and histological alterations similar to those of
Parkinson’s disease in rats. However, only a subset of animals show these
effects and it is unclear whether more subtle alterations are caused by chronic
administration of rotenone in those animals that appear resistant to its toxic
effects on dopaminergic nerve terminals. To address this question, vehicle or
rotenone (2.0, 2.5, or 3.5 mg/kg/day) was administered intravenously or
subcutaneously for 21 days to adult rats, and rotenone effects on survival,
motor behavior, and striatal tyrosine hydroxylase immunoreactivity (TH-IR) were
examined. Both intravenous and subcutaneous rotenone induced a dose-dependent
decrease in survival rates. Surviving animals showed a decrease in spontaneous
rearing. Locomotor activity and movement initiation time were also altered in
some of the experimental groups. Confirming previous results, TH-IR in the
striatum was markedly decreased in rats that fell ill early in the study and in
a few of the surviving rats with high rotenone doses. However, none of the
surviving rats receiving 2.0 mg/kg/day showed TH-IR loss reminiscent of
Parkinson’s disease, and loss of striatal TH-IR across doses was not correlated
with motor behavior in individual rats. Thus, chronic administration of low
doses of rotenone induces motor anomalies even in animals that do not develop
histological signs of Parkinson’s disease, indicating a pervasive neurological
effect of moderate mitochondrial dysfunction in vivo.
DOI: 10.1016/j.expneurol.2004.01.023
PMID: 15144868 [Indexed for MEDLINE]