Early life arsenic exposure and brain dopaminergic alterations in rats

•Impact of early life arsenic exposure investigated on brain dopaminergic alterations.•Arsenic increased DA-D2 receptors in corpus striatum associated with hyperactivity.•Dopaminergic alterations linked with mitochondrial dysfunctions and enhanced apoptosis.•Behavioral and neurochemical changes persisted on withdrawal of exposure in rats.•Arsenic exposure during development of brain dopamine receptors appears critical. Recently, we found that early life exposure to arsenic at low doses resulted to cause brain cholinergic deficits and exhibited a trend of recovery on withdrawal of arsenic exposure. In continuation to this, the present study has been carried out to assess the impact of low level arsenic exposure on brain dopaminergic system and associated behavior in developing rats and investigate if neurobehavioral changes are recovered or persistent. Early life exposure (PD22–PD59) to arsenic (2 or 4mg/kg body weight, p.o.) in rats resulted to increase the motor activity on PD60, compared to controls. The hyperactivity in arsenic exposed rats was found to be linked with increase in the binding of DA-D2 receptors (38%, 56%), mRNA expression of DAR-D2 receptor gene (68%, 97%) and expression of tyrosine hydroxylase protein (1.93, 2.73-fold) in the corpus striatum as compared to controls on PD60. Exposure to arsenic enhanced generation of ROS (47%, 84%) and was associated with decrease in the mitochondrial membrane potential (13.3%, 15.33%), activity of mitochondrial complexes and increased oxidative stress. Disruption in the expression of pro-apoptotic, anti-apoptotic and stress marker proteins was also distinct in the corpus striatum of arsenic exposed rats. The severity of changes in the behavioral and neurochemical endpoints were found to persist in rats exposed to arsenic at high dose and exhibited a trend of recovery at low dose on withdrawal of arsenic exposure on PD90. Early life arsenic exposure appears to be critical and vulnerable as development of dopamine receptors continues during this period.