Ontogenetic manganese exposure with perinatal 6-OHDA lesioning alters behavioral responses of rats to dopamine D1 and D2 agonist treatments

• The effect of perinatal manganese exposure in a 6-hydroxydopamine rat model of Parkinson's disease was studied.
• Both dopamine and its metabolite homovanilic acid were reduced in rats lesioned with 6-hydroxydopamine.
• Co-exposure to perinatal manganese did not intensify neurotransmission disturbances.
• Manganese did not further damage neurotransmitter activity in the neostriatum, although ontogenetic exposure to manganese enhances the behavioral toxicity to 6-hydroxydopamine.

The effect of neonatal manganese (Mn) exposure in a 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease was investigated. Pregnant Wistar rats were given drinking water with 10,000 ppm of Manganese (MnCl2.4H2O) from the time of conception until weaning on the 21st day after delivery. Control rats consumed tap water. Three days after the birth, other groups of neonatal rat pups were pretreated with desipramine (20 mg/kg ip 1 h) prior to bilateral ICV administration of 6-OHDA or its vehicle, saline–ascorbic (0.1%) (control). Two months after the birth, striatal dopamine and homovanilic acid efflux measured by an in vivo microdialysis method were reduced in rats lesioned with 6-OHDA. Co-exposure to perinatal Mn did not modify neurotransmission alterations. However, there were prominent abnormalities in behavioral testing in rats perinatally exposed to Mn and treated neonatally with 6-OHDA. These findings demonstrate that although Mn did not further damage neurotransmitter activity in the neostriatum, ontogenetic exposure to Mn enhances the behavioral toxicity to 6-OHDA.