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

• Published in: Toxicological sciences Vol. 169; no. 2; pp. 511 - 523
• Main Authors: Pitzer, Emily M, Sugimoto, Chiho, Gudelsky, Gary A, Huff Adams, Courtney L, Williams, Michael T, Vorhees, Charles V
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01-06-2019
• Subjects: Animals; Body Weight - drug effects; Cognition - drug effects; Deltamethrin and Cognitive Function in Rats; Female; Hippocampus - drug effects; Hippocampus - physiology; Insecticides - toxicity; Learning - drug effects; Long-Term Potentiation - drug effects; Male; Maze Learning - drug effects; Nitriles - toxicity; Pyrethrins - toxicity; Rats; Rats, Sprague-Dawley; Reflex, Startle - drug effects; deltamethrin; pyrethroids; development; rats; cognition
• ISSN: 1096-6080; 1096-0929
• DOI: 10.1093/toxsci/kfz067

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.