Diisopropylfluorophosphate administration in the pre-weanling period induces long-term changes in anxiety behavior and passive avoidance in adult mice

Abstract

The developing brain may be particularly vulnerable to exposure to acetylcholinesterase (AChE) inhibitors because of the role of AChE on neuronal development and the effects of cholinergic pathways in mediating behavioral and hormonal responses to stress. C57BL/65 mice of both sexes were injected with 1 mg/kg s.c. diisopropylfluorophosphate (DFP) or saline in three separate experiments, on postnatal days (PNDs) 4-10, 14-20, or 30-36. Anxiety and conditioned avoidance were assessed on the elevated-plus maze (EPM) and step-down passive avoidance (PA) paradigms, respectively, at age 4-5 months. In addition, locomotion and reactivity to pain on the hot plate were assessed. Mice treated on PNDs 4-10 or PNDs 14-20 spent relatively more time and made more entries to the open arms on the first, but not second, exposure to the EPM. Females, but not males, treated with DFP showed deficits in PA retention after 24 h when treated on PNDs 4-10 and on PNDs 14-20. Mice treated on PNDs 30-36 were not impaired in either behavior. Administration of DFP in the preweanling period did not affect locomotor activity or pain reactivity. The results suggest that preweanling exposure to DFP results in anxiolysis in novel conflict situations but exacerbated context-enhanced anxiety.