Comparison of two methods of administration of amphetamine on the dynamics of dopaminergic neurons in the rat.

Dopamine (DA) and its metabolite dihydroxyphenylacetic acid (DOPAC) in brain were examined in the striatum and nucleus accumbens septi after the administration of amphetamine by two different methods. A computer-controlled device was constructed to deliver intravenous injections of amphetamine in patterns mimicking those of animals in a self-administration paradigm, i.e. a total of 65 injections of 0.125 mg/kg/injection over 8 hr [total; 8.13 mg/kg (22.05 mumoles/kg)]. The second method was the intraperitoneal injection of 8.13 mg/kg as a single bolus. Control animals were intravenously or intraperitoneally administered saline. The effects of the two injection methods on the concentrations of DA and DOPAC were quite distinct at early times. This may in part be due to differences in the peak concentrations of amphetamine in brain achieved by the two regimens. Differences still persisted 48 hr after injection, particularly in the striatum. Increased levels of DA and DOPAC were observed at this time after the computer-controlled injections, while significantly decreased DA in the striatum is found after intraperitoneal bolus injections. These data strongly suggest that the method of administration of amphetamine can substantially alter the effects and possible toxicity of the drug on dopaminergic systems.