A threshold neurotoxic exposure to amphetamine disrupts cortical synaptic neuroplasticity.
Bowyer-JF; Pogge-AR; Delongchamp-RR; O'Callaghan-JP; Patel-KM; Vrana-KE; Freeman-WM
Toxicologist 2006 Mar; 90(1):495
A 9 day exposure to D-amphetamine (AMPH), at a "threshold" necessary to produce histological signs of neurotoxicity, was evaluated for its effects on genes that are normally upregulated by amphetamine or methamphetamine "challenges". cDNA arrays and RT-PCR were used to evaluate the changes in gene expression. Male rats were exposed for 9 days to either 3 X 1ml/kg saline, 3 X 2 mg/kg AMPH (Low Dose AMPH) or of 3 X 7.5 mg/kg AMPH (High Dose), with 6 hr between doses, per day. The environmental temperature was held at 17 C to prevent AMPH-induced hyperthermia. The groups were challenged with either saline or 7.5 mg/kg AMPH on the 10th day, and gene expression profiles at 3 hr post challenge were determined in striatum and parietal cortex. The AMPH challenge resulted in a significantly and substantially lesser increase in the expression of activityrelated cytoskeletal protein (ARC) and nerve growth-factor inducible proteins (NGFI-A & B) in the parietal cortex of the High Dose AMPH group compared to the Saline or Low Dose AMPH group challenged with AMPH. In contrast, in the striatum there was either no difference or a slight increase in the upregulation of these genes after the AMPH challenge in the High Dose AMPH animals. These results show that within the parietal cortex the disruption of genes involved in the synaptic formation processes is sensitive to threshold neurotoxic AMPH exposures, and that the learning processes in this region may be compromised.
Neurotoxins; Neurotoxicology; Neurotoxicity; Neurotoxic-effects; Exposure-levels; Exposure-assessment; Laboratory-animals; Animals; Animal-studies; Temperature-effects
The Toxicologist. Society of Toxicology 45th Annual Meeting and ToxExpo, March 5-9, 2006, San Diego, California