Deltamethrin Exposure Daily From Postnatal Day 3–20 in Sprague-Dawley Rats Causes Long-term Cognitive and Behavioral Deficits

Abstract

Pyrethroids are synthetic insecticides that act acutely on voltage gated sodium channels to prolong channel opening and depolarization. Epidemiological studies find that exposure to pyrethroids are associated with neurological and developmental abnormalities in children. The long-term effects of type II pyrethroids, such as deltamethrin (DLM), on development have received little attention. We exposed Sprague-Dawley rats to DLM by gavage at doses of 0, 0.25, 0.5, and 1.0 mg/kg/day from postnatal day (P) 3-20 in a split-litter design. Following behavioral testing as adults, monoamine levels, release, and mRNA were assessed via high performance liquid chromatography, microdialysis, and qPCR, respectively. Long-term potentiation (LTP) was assessed at P25-35. Developmental DLM exposure resulted in deficits in allocentric and egocentric learning and memory, increased startle reactivity, reduced conditioned contextual freezing, and attenuated MK-801 induced hyperactivity compared with controls. Startle and egocentric learning were preferentially affected in males. Deltamethrin-treated rats exhibited increased CA1 hippocampal LTP, decreased extracellular dopamine release by microdialysis, reduced dopamine D1 receptor mRNA expression in neostriatum, and decreased norepinephrine levels in the hippocampus. The data indicate that neonatal DLM exposure has adverse long-term effects on learning, memory, startle, glutamatergic function, LTP, and norepinephrine.

Whole brain proton irradiation in adult Sprague Dawley rats produces dose dependent and non-dependent cognitive, behavioral, and dopaminergic effects

“…Performance in the CWM is largely mediated by dopamine since dopamine lesions of the striatum with 6-hydroxydopamine induce large learning deficits 25,48,49 . Drugs, pesticides, or metals that target the striatum also produce deficits in the CWM [50][51][52][53][54][55] . This is the first study to show long-term deficits in the CWM following irradiation.…”

Effect of Lambdacyhalothrin on Locomotor Activity, Memory, Selected Biochemical Parameters, Tumor Necrosis Factor α, and Interleukin 1ß in a Mouse Model

“…They also modulate the level of neurotransmitters: gamma-aminobutyric acid (GABA) and dopamine [ 10 , 11 , 12 ]. In humans, high doses of LCH cause excessive salivation, fatigue, coughing, and abdominal pain [ 13 , 14 , 15 ].…”

Effect of long‐term treatment with a mixture of pyrethroids on the expression of genes that govern male germ cell production in rats

“…[ 5 ] In humans, pyrethroid toxicity is implicated to induce the motor deficiency associated with the central nervous system and Parkinson's disease. [ 6‐8 ] In murine models, pyrethroids cause cognitive defects, [ 9 ] alterations in the levels of GABA, 3, 4‐dihydroxyphenylacetic acid, and noradrenaline [ 10 ] dopaminergic neurodegradation [ 11 ] and alterations in xenobiotic enzyme levels of the brain. [ 12 ] Pyrethroid toxicity in other organ systems is reported as well.…”