Mice were treated with 1-methyl-4-
phenyl-1,2,3,6-tetrahydropyridine (MPTP; 30 mg/kg
i.p. twice, 16 h apart). This resulted in changes in
motor performance and toxic insult of nigral neurons
as evidenced by dopamine depletion in nucleus caudatus
putamen. In vitro and in vivo treatment of
MPTP caused the generation of hydroxyl radicals
(•OH) as measured by a sensitive salicylate hydroxylation
procedure. A dopamine agonist, bromocriptine
(10 mM and 10 mg/kg i.p.), blocked •OH formation
caused by MPTP in vitro (20 mM) and in vivo
(30 mg/kg i.p.). An MPTP-induced increase in the
activity of catalase and superoxide dismutase in substantia
nigra on the seventh day was reduced by bromocriptine
pretreatment. Bromocriptine blocked
MPTP-induced behavioral dysfunction as well as
glutathione and dopamine depletion, indicating its
potent neuroprotective action. This study suggests
that bromocriptine stimulates antioxidant mechanisms
in the brain and acts as a free radical scavenger
in addition to its action at dopamine receptors,
thus indicating its strength as a valuable neuroprotectant.
—Muralikrishnan, D., Mohanakumar,
K. P. Neuroprotection by bromocriptine against 1-
methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced
neurotoxicity in mice