title: Decreased anxiety in juvenile rats following exposure to low levels of chlorpyrifos during development.
abstract: Exposure to chlorpyrifos (CPF) during the late preweanling period in rats inhibits the endocannabinoid metabolizing enzymes fatty acid hydrolase (FAAH) and monoacylglycerol lipase (MAGL), resulting in accumulation of their respective substrates anandamide (AEA) and 2-arachidonylglycerol (2-AG). This occurs at 1.0mg/kg, but at a lower dosage (0.5mg/kg) only FAAH and AEA are affected with no measurable inhibition of either cholinesterase (ChE) or MAGL. The endocannabinoid system plays a vital role in nervous system development and may be an important developmental target for CPF. The endocannabinoid system plays an important role in the regulation of anxiety and, at higher dosages, developmental exposure to CPF alters anxiety-like behavior. However, it is not clear whether exposure to low dosages of CPF that do not inhibit ChE will cause any persistent effects on anxiety-like behavior. To determine if this occurs, 10-day old rat pups were exposed daily for 7 days to either corn oil or 0.5, 0.75, or 1.0mg/kg CPF by oral gavage. At 12h following the last CPF administration, 1.0mg/kg resulted in significant inhibition of FAAH, MAGL, and ChE, whereas 0.5 and 0.75mg/kg resulted in significant inhibition of only FAAH. AEA levels were significantly elevated in all three treatment groups as were palmitoylethanolamide and oleoylethanolamide, which are also substrates for FAAH. 2-AG levels were significantly elevated by 0.75 and 1.0mg/kg but not 0.5mg/kg. On day 25, the latency to emerge from a dark container into a highly illuminated novel open field was measured as an indicator of anxiety. All three CPF treatment groups spent significantly less time in the dark container prior to emerging as compared to the control group, suggesting a decreased level of anxiety. This demonstrates that repeated preweanling exposure to dosages of CPF that do not inhibit brain ChE can induce a decline in the level of anxiety that is detectable during the early postweanling period.
authors.affiliation: Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762-6100, USA. Electronic address: rlcarr@cvm.msstate.edu.
authors.forename: Russell L
authors.initials: RL
authors.lastname: Carr
authors.affiliation: Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762-6100, USA.
authors.forename: Nathan H
authors.initials: NH
authors.lastname: Armstrong
authors.affiliation: Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762-6100, USA.
authors.forename: Alenda T
authors.initials: AT
authors.lastname: Buchanan
authors.affiliation: Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762-6100, USA.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Eells
authors.affiliation: Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762-6100, USA.
authors.forename: Afzaal N
authors.initials: AN
authors.lastname: Mohammed
authors.affiliation: Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762-6100, USA.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Ross
authors.affiliation: Center for Environmental Health Sciences, Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762-6100, USA.
authors.forename: Carole A
authors.initials: CA
authors.lastname: Nail
mesh_terms: D000375:Aging / Q000187:drug effects*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000188:drug therapy*; D001095:Arachidonic Acids / Q000378:metabolism; D004390:Chlorpyrifos / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D002802:Cholinesterases / Q000378:metabolism; D015331:Cohort Studies; D004195:Disease Models, Animal; D063388:Endocannabinoids / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D008297:Male; D009829:Oleic Acids / Q000627:therapeutic use; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors
chemical_list: D001095:Arachidonic Acids; D002800:Cholinesterase Inhibitors; D063388:Endocannabinoids; D009829:Oleic Acids; D053284:Polyunsaturated Alkamides; C488250:oleoylethanolamide; D002802:Cholinesterases; D004390:Chlorpyrifos; C078814:anandamide
keywords: Anxiety; Chlorpyrifos; Developmental; Endocannabinoid; Organophosphate insecticides