Developmental exposure to chlorpyrifos and diazinon differentially affect passive avoidance performance and nitric oxide synthase-containing neurons in the basolateral complex of the amygdala

Chronic exposure to low doses of organophosphates during brain development can induce persistent neurochemical and behavioral effects. This study sought to determine the long-lasting effects of developmental exposure to chlorpyrifos (CPF) and diazinon (DZN) on passive avoidance (PA) performance and neuronal nitric oxide synthase (nNOS)-containing neurons in the subnuclei within basolateral complex of amygdala (BLC). Developing rats were exposed to daily dose (1 mg/kg) of CPF or DZN during gestational days 15–18 and postnatal days (PND) 1–4. PA performance was assessed in young adulthood (PND 60). Brain sections were also processed by NADPH-diaphorase (NADPH-d) and nNOS immunohistochemistry. Gestational exposure to CPF increased NADPH-d+/nNOS-immunoreactive (IR) neurons within the basolateral nucleus (BL) and medial paracapsular intercalated cluster, which was along with PA retention impairment in both male and female rats. Prenatal exposure to DZN did not significantly change the number of NADPH-d+/nNOS-IR neurons in the BLC while impaired PA retention in females. Postnatal exposure to CPF decreased NADPH-d+/NOS-IR neurons in the BL without affecting PA performance. Exposure to DZN during early postnatal period impaired PA retention in both sexes, albeit to a lesser extent in females, and was along with a considerable sex independent reduction of NADPH-d+/NOS-IR neurons in all BLC subnuclei. Our data suggest that developmental exposure to apparently subtoxic dose of CPF and DZN elicit long-lasting impairment in PA retention that are associated, but not necessarily correlated with effects on NADPH-d+/NOS-IR neurons in BLC of the amygdala.

► Developing rats were exposed to low doses of chlorpyrifos and diazinon.
► Chlorpyrifos impaired passive avoidance retention in a time dependent manner.
► Diazinon-induced passive avoidance impairment was time and sex dependent.
► These agents affected NOS-containing neurons in the amygdaloid basolateral complex.
► The effects on NOS-containing neurons were irrelevant of sex but dependent to agent and time.