Long-Term Fipronil Treatment Induces Hyperactivity in Female Mice

Abstract

Fipronil is an insecticide widely used for veterinary and agricultural purposes. While its insecticidal properties mostly rely on its high affinity antagonistic activity on insect γ aminobutyric acid (GABA) receptors, fipronil and its main metabolite fipronil sulfone nevertheless display non-negligible affinity for mammalian GABA A receptor. As several environmental toxicants have been shown to raise the risk of developing various neurodegenerative disorders, the aim of this study was to evaluate whether long-term low dose administration of fipronil could lead to cognitive deficiencies. Our results indicate that long-term fipronil treatment leads to behavioral perturbations in mice, indicating an accumulative effect of sustained exposure to low dose of fipronil. Although no memory impairment was observed during the course of our study, we noticed a significant hyperlocomotion behavior after 43 weeks of weekly fipronil administration, which is consistent with its direct effect on the GABAergic system.

Tolerance of Biopronil Spot on^® after repeated single- or multiple-dose topical treatments in dogs

“…As mentioned earlier, FIP and fipronil sulfone (FIP main metabolite) act as inhibitors of insect GABA receptors and prevent GABA binding to its receptor, blocking the inhibitory function of GABA in the central nervous system and, thus, leading, at low doses, to neuronal hyperexcitation and, at high doses, to the paralysis and death of insects (Koslowski et al 2020). Fipronil has a notably higher affinity for insect GABA receptors than for mammalian GABA receptors (Hainzl et al 1998).…”

“…Both FIP and fipronil sulfone are able to cross the blood-brain barrier in rats and mice (Hainzl et al 1998;Cravedi et al 2013). A recent study, evaluating the long-term low dose administration of FIP in mice and its relation to cognitive deficiencies showed that a 48-week-FIP treatment leads to behavioural perturbations, indicating an accumulative effect of sustained exposure to low doses of FIP (Koslowski et al 2020). In the present study, no significant symptoms specific to the nervous system were observed over the whole experiment.…”

“…-trifluoromethylphenyl)-4-fluoromethylsulfinyl pyrazole] (FIP) is a second-generation phenylpyrazole insecticide used in veterinary medicine for https://doi.org/10.17221/6/2021-VETMED the control of ectoparasites (Tingle et al 2003). FIP blocks the gamma-aminobutyric acid (GABA)gated chloride channels of neurons in the central nervous system, resulting in the hyper-excitation of the central nervous system and death (Koslowski et al 2020). GABA-gated chloride channels are expressed in the central nervous system of both vertebrates and invertebrates, nevertheless, the specificity of FIP for insect GABA chloride channels is 700 to 1 300 times greater than in mammals and permits the selective control of invertebrate ectoparasitic hosts on the target species, such as dogs and cats (Zhao et al 2003;Zhao et al 2004).…”

Fipronil use and associated effects on hematological and biochemical parameters of blue land crab (Cardisoma guanhumi Latreille): Ecological implication

“…For example, the LC 50 for fipronil in African clawed frog ( X. laevis ) tadpoles was 850 μg/L; the LC 50 s for bluegill sunfish ( Lepomis macrochirus ) and rainbow trout ( Oncorhynchus mykiss ) were 85 and 248 μg/L, respectively (Wang et al, 2019). An oral LD 50 for fipronil in rats was 97 mg/kg, but a dermal LD 50 was 2 g/kg in the same species (Koslowski et al, 2020). An acute dermal LD 50 in rabbits was 354 mg/kg.…”

“…An acute dermal LD 50 in rabbits was 354 mg/kg. Five‐day dietary LC 50 s for bobwhite quail and mallard ducks were 49 mg/kg and 5 g/kg, respectively (Koslowski et al, 2020). LC 50 s for midges ( Chironomus dilutus ), mysid shrimp ( Neomysis americana ), grass shrimp ( Palaemonetes pugio ), black flies ( Simulium vittatum ), and Daphnia were 0.082, 0.14, 0.32, 0.18–0.31, and 190 μg/L, respectively (CDC, 2005; Maeda et al, 2021).…”