| Description |
The central neurochemical effects of chronic low doses (0.5 or 5 mg/kg s.c., every 12 h for 2 wk) if d-amphetamine (AMPH) were studied in rats of varying ages. Tyrosine hydroxylase (TH) and tryptophan hydroxylase (TPH) activities in neostriata of male offspring of dams exposed to 5 mg/kg AMPH during gestation showed significant depressions at 3 weeks of age, while corresponding neurotransmitters were at control levels. In contrast, the striatal enzyme activities in the dams were normal, but significant depressions were observed in the levels of striatal 5-hydroxytryptamin (5-HT), 5-hydroxyindoleacetic acid 5-HIAA, dopamine (DA) 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA). All parameters returned to normal by 7 weeks. Neurochemical changes were minimal in juvenile and adult males subjected to the same AMPH dosing regimen. The hypothalamic concentrations of 5-HT, 5-HIAA, and DA in adult males were reduced at 16 h, but these parameters were unaffected in the juveniles. Recovery in the adults was complete by 3 wks post dosing. Not effects were seen with the lower dose of AMPH (0.5 mg/kg) in any age group. The chronic doses of AMPH used in this study are not as toxic to the central serotonergic or dopaminergic systems of the rat as higher doses that have previously been studied in acute and subacute dosing regimens. Under these condition, the age of the animal at the time of drug exposure did not significantly alter the severity of the toxicity that was observed. Further, our data suggest that that Neurotoxicity of AMPH is highly depend on dose and duration of exposure. |
