The pesticide fipronil injected into the substantia nigra of male rats decreases striatal dopamine content: A neurochemical, immunohistochemical and behavioral study

Rahul Bharatiya, Jessica Bratzu, Carla Lobina, Giulia Corda, Cristina Cocco, Philippe De Deurwaerdere, Antonio Argiolas, Maria Rosaria Melis, Fabrizio Sanna
Behavioural Brain Research. 2020-04-01; 384: 112562
DOI: 10.1016/j.bbr.2020.112562

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Experimental evidence shows that the phenylpyrazole pesticide fipronil exerts
neurotoxic effects at central level in rodents, and in particular on
nigrostriatal dopaminergic neurons, whose degeneration is well known to cause
motor and non-motor deficits in animals and in humans. In order to characterize
better the central neurotoxic effect of fipronil, we injected fipronil (15 and 25
μg) dissolved in dimethyl sulfoxide (DMSO) unilaterally into the substantia nigra
of male rats. Male rats injected with DMSO unilaterally into the substantia nigra
were used as controls. Control and fipronil-treated rats were then tested in
different motor (i.e., open field arena, rotarod, tail flick) and non motor tests
(novel object recognition, social interaction) 15 days after injection. A
systemic challenge dose of the dopamine-agonist apomorphine was also used to
study the presence of a rotational behavior. Sixteen days after fipronil or DMSO
injection into the substantia nigra, rats were sacrificed, and either striatal
dopamine content or substantia nigra tyrosine hydroxylase (TH) immunoreactivity
were measured. The results confirm that the unilateral injection of fipronil into
the substantia nigra caused the degeneration of nigrostriatal dopaminergic
neurons, which leads to a decrease around 50 % in striatal dopamine content and
substantia nigra TH imunoreactivity. This occurred together with changes in motor
activity and coordination, and in nociception but not in recognition memory and
in social interaction, as revealed by the results of the behavioral experiments
performed in fipronil-treated rats compared to vehicle-treated rats 15 days after
treatment, as found with other compounds that destroy nigrostriatal dopaminergic


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