EXPOSURE TO AN ORGANOPHOSPHATE (DFP) DURING A DEFINED PERIOD IN NEONATAL LIFE INDUCES PERMANENT CHANGES IN BRAIN MUSCARINIC RECEPTORS AND BEHAVIOR IN ADULT MICE

The organophosphate Diisopropylfluorophosphate (DFP) is a well-known i nhibitor of cholinesterases. We have recently observed that neonatal e xposure to a single subsymptomal dose of DFP induces permanent alterat ions in muscarinic cholinergic receptors (MAChRs) and in spontaneous b ehaviour, in the mice as adults.In order to determine if there is a cr itical period for these effects, neonatal mice were given a single ora l dose of 1.5 mg/kg DFP b.wt. on postnatal day 3, 10 or 19, causing eq ual inhibition of AChE. At the adult age of 4 months the mice were tes ted for spontaneous motor behaviour, and were subsequently sacrificed for measurement of density of MAChRs and subpopulations of MAChRs in t he cerebral cortex by using the antagonist quinuclidinyl benzilate ([H -3]QNB), and agonist carbachol, respectively. At adult age, mice expos ed to DFP on postnatal day (PND) 3 or 10 showed significant (P less th an or equal to 0.01) alterations in spontaneous motor behaviour and a significant (P less than or equal to 0.01) decrease in muscarinic rece ptor density. There were no alterations mice exposed on PND 19. The pr oportions and affinity-constants of high- and low-affinity MAChR bindi ng sites were not affected in mice showing altered MAChR density. The lack of effect on mice exposed on PND 19 was not due to differences in AChE activity.