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

•Fipronil injected in the substantia nigra of male rats induces changes in several behaviors.•Among these are changes in spontaneous motor activity and motor coordination.•The pesticide also induces changes in nociception and object recognition performance.•These changes are parallel to decreases in...

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Bibliographic Details
Published in:	Behavioural brain research 2020-04, Vol.384, p.112562, Article 112562
Main Authors:	Bharatiya, Rahul, Bratzu, Jessica, Lobina, Carla, Corda, Giulia, Cocco, Cristina, De Deurwaerdere, Philippe, Argiolas, Antonio, Melis, Maria Rosaria, Sanna, Fabrizio
Format:	Article
Language:	eng
Subjects:	Animals Apomorphine - pharmacology Corpus Striatum - drug effects Corpus Striatum - metabolism Dopamine Dopamine - metabolism Dopamine Agonists - pharmacology Fipronil Immunohistochemistry Insecticides - toxicity Locomotion - drug effects Male Motor activity Motor Activity - drug effects Nociception Nociception - drug effects Novel object recognition Open Field Test Pyrazoles - toxicity Rats Recognition, Psychology - drug effects Rotarod Performance Test Social interaction Social Interaction - drug effects Substantia Nigra - drug effects Substantia Nigra - metabolism Tyrosine 3-Monooxygenase - drug effects Tyrosine 3-Monooxygenase - metabolism
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Summary:	•Fipronil injected in the substantia nigra of male rats induces changes in several behaviors.•Among these are changes in spontaneous motor activity and motor coordination.•The pesticide also induces changes in nociception and object recognition performance.•These changes are parallel to decreases in striatal dopamine and nigral tyrosine hydroxylase. 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 neurons.
ISSN:	0166-4328 1872-7549