Developmental Chlorpyrifos and Methyl Parathion Exposure Alters Radial-Arm Maze Performance in Juvenile and Adult Rats

Abstract

Although the use of organophosphate (OP) insecticides has been restricted, sufficient exposure can occur to induce detrimental neurobehavioral effects. In this study, we measured physical and reflex development and spatial learning and memory in rats repeatedly exposed to incremental doses of chlorpyrifos (CPS) and methyl parathion (MPS) from postnatal day (PND) 1 to PND21. Other than decreased body weight in the higher dosage groups, no effects on physical or reflex development were observed. Significant hippocampal cholinesterase inhibition was induced in all treatment groups for up to 19 days following exposure. Beginning on PND36, working and reference memory was tested using a 12-arm radial maze, with subject animals trained and tested 4 days a week for 4 weeks. In males, working memory was decreased with the medium and high dosage of MPS but only the high dosage of CPS; while in females, no deficits were observed. For reference memory, errors were significantly increased in males exposed to the high dosage of CPS and all dosages of MPS. In females, enhanced performance was observed within the medium and high dosages of CPS but not with MPS. These data show that repeated developmental exposure to OP insecticides can induce sex-selective alterations and long-lasting changes in spatial learning and memory formation when measured using a radial arm maze and that MPS and CPS induce different neurobehavioral outcomes.

Acetylcholinesterase Activity and Neurodevelopment in Boys and Girls

“…Considering that the cholinergic system plays an important role in brain development, 36,37 and subclinically lower AChE activity has been associated with measureable physiologic changes in children, 38 our findings support the hypothesis that AChE inhibition is an important mechanism of neurotoxicity of cholinesterase inhibitor pesticides. Chlorpyrifos has been reported to inhibit brain AChE activity in rats, [16][17][18][19] with significant AChE inhibition in the hippocampus, 20 a structure with important roles in memory, spatial navigation, imagination, and perhaps inhibitory control. [39][40][41] However, AChE inhibition is an indicator of exposure, and other neurotoxic mechanisms may also be present.…”

“…Next, erythrocytic AChE is similar to neuronal AChE activity, 2 and brain AChE has been reported to be diminished after chlorpyrifos exposure in rats. [16][17][18][19][20] In addition, erythrocytic AChE has a long recovery time (82 days), 21 low intraindividual variability, 22 and is considered to be a stable assessment of past exposures to cholinesterase inhibitors, 23 although it is less sensitive and specific than most pesticide quantification methods. 23,24 Finally, we previously found that a single measure of AChE activity can be an adequate indicator of pesticide exposure in epidemiologic studies of children.…”

The Red Blood Cell Acetylcholinesterase Levels of Depressive Patients with Suicidal Behavior in an Agricultural Area

“…Prenatally organophosphate exposed children had greater decreases in attention among boys versus girls in agricultural areas in California [30] and in working memory among children in New York City [31]. Animal studies have also determined greater detrimental neurochemical and behavioral effects among males after exposure to organophosphates [32].…”

“…Synaptic and erythrocytic AChE are functionally similar so changes in erythrocytic AChE activity may reflect the situation in target tissues, especially in the brain. OPs has been reported to inhibit brain AChE activity in rats with significant AChE inhibition in the hippocampus [32]. Hippocampus is a structure with important roles in depression, suicidal events, memory and imagination [34].…”

“…Because AChE inhibition is a physiologic reaction to OPs exposure and AChE levels is not affected by OPs metabolism and individual's sensitivity. Erythrocytic and neuronal AChE has similar activity and brain AChE has been reported to be derogated after chlorpyrifos exposure in rats [14,32]. And also erythrocytic AChE has a long salvage time (82 days) [15], intraindividual changeability is low [40], is taken into account as a stable appraisal of past exposures to cholinesterase inhibitors [41].…”