Increased sensitivity in dopamine D(2)-like brain receptors from 2,4-dichlorophenoxyacetic acid (2,4-D)-exposed and amphetamine-challenged rats.

To determine whether the dopamine D(2) receptor plays a crucial role in chemically acquired sensitivity to drugs of abuse like amphetamine (AMPH) after an exposure to aryloxoalkanoic compounds, we examined in the present work the impact of AMPH (10 mg/kg, i.p.) on the dopaminergic D(2)-like receptors. Rats were exposed to 2,4-D 70 mg/kg/day from gestation day (GD) 16 to postnatal day (PND) 23. After weaning, the pups were assigned to one of the two subgroups: T1 (fed with untreated diet until PND 90) and T2 (maintained with 2,4-D diet until PND 90). After that, an acute challenge with AMPH was administered to each animal. Rats were sacrificed at 0, 5, 24, 72, and 168 h after AMPH, and membranes of striatum (CPu), prefrontal cortex (PfC), hippocampus (H), and cerebellum (Ce) were obtained. Binding studies employing [(3)H]nemonapride showed that AMPH caused an increase in DA D(2)-like receptors of all brain areas between 5 and 24 h after the treatment, with a reduction to the basal levels one week later. The AMPH challenge to (T1 and T2) 2,4-D-exposed rats showed an alteration on receptor density depending on brain area and on sex, more than on the 2,4-D exposure time. This D(2)-like receptor density increase could explain the exacerbated behaviors of the 2,4-D-exposed and amphetamine-challenged animals, as previously observed by us. The withdrawal of 2,4-D did not produce a real reversion to basal levels of D(2)-like receptors, indicating that herbicide exposure during the preweanling period caused a sensitization and a stable DA D(2)-like receptor increase that was elicited when the system was challenged with this dopaminergic drug.