Regionally specific changes in central brain monoamine levels by 2,4-dichlorophenoxyacetic acid in acute treated rats.

As reported in our previous studies, "Serotonin Syndrome", rearing and circling behaviors, were the responses of rats treated with the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) and challenged with amphetamine. An altered serotonergic and dopaminergic system may be responsible for these behaviors. In this work, endogenous levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-HT), and 5-hydroxyindolacetic acid (5-HIAA) were measured in the areas of the mesocortico-limbico and nigrostriatal systems of rats treated with 50 or 100 mg/kg of 2,4-D, but also challenged with amphetamine (5 or 10 mg/kg), in order to determine regional brain contents of biogenic amines and their metabolites and to find a correlation with the behaviors described. The prefrontal cortex (PFc), striatum, nucleus accumbens (NA), midbrain, ventral tegmental area (VTA), substantia nigra (SN) and cerebellum were assayed. The herbicide 2,4-D increased the 5-HT and DA basal levels and these increments were dependent on sex, brain area and 2,4-D doses. The challenge with 5 or 10 mg/kg amphetamine to 2,4-D (50 or 100 mg/kg) treated rats also resulted in an area-, sex- and dose-dependent alterations of the 2,4-D effect on dopaminergic and serotonergic systems. We are demonstrating a correlation between rat behavior altered by the herbicide's treatment and the contents of 5-HT and DA in brain areas, such as PFc, VTA, SN, striatum, NA, midbrain and cerebellum. In order for 2,4-D to produce the neurobehavioral alterations, not only are high levels of 5-HT and DA necessary, but these neurotransmitters must be released.