Effects of 2,4-dichlorophenoxyacetic acid exposure on dopamine D2-like receptors in rat brain

2,4-Dichlorophenoxyacetic acid (2,4-D), a worldwide-used herbicide, has been associated with a range of adverse health effects on humans and different animal species. Although the mechanism of 2,4-D neurotoxicity remains unknown, we had previously reported changes in various neurotransmitter systems, such as serotonin (5-HT) and dopamine (DA), which were proposed to mediate some of the behavioral effects in rats. In the present work, we examined the impact of 2,4-D exposure on the ontogeny of dopaminergic D2-type receptors in prefrontal cortex (PFc), striatum (CPu), hippocampus (H) and cerebellum (Cer). Pregnant rats were orally exposed to 70 mg/kg/day of 2,4-D from gestation day (GD) 16 to postpartum day 23. After weaning, the pups were assigned to one of the two subgroups: T1 [fed with untreated diet until postnatal day, (PD) 90] and T2 [maintained with 2,4-D diet until PD 90]. Five to eight pups per age and sex were sacrificed at 6, 15, 30, 45 or 90 days of age for membrane receptor binding assays employing [3H]nemonapride. Subchronic 2,4-D exposure (T2 group) increased DA D2-type receptor around 40% in CPu. In addition, DA D2-type receptor levels also increased in PFc (15 and 30 days) and Cer (30 and 90 days). Sex-dependent differences in D2 receptors were observed with T2 female rats being more affected than T2 male rats. When the herbicide treatment was interrupted after weaning (T1 group), DA D2-type receptor density was apparently recovered and stabilized to control level. These findings suggest a reversible vulnerability of D2-type receptors to 2,4-D exposure. Regional increases of D2-type receptor density may explain certain behaviors reported early by us, such as catalepsy and right-turning preference in rats exposed to 2,4-D.