Effects of acute and long-term treatment with amphetamine on evoked responses and long-term potentiation in the dentate gyrus of anesthetized rats.

We examined the effects of D-amphetamine (AMP) on evoked responses and long-term potentiation (LTP) in the dentate gyrus of rats in 4 different conditions: untreated + saline, untreated + acute AMP, long-term AMP-treated + saline, and long-term AMP-treated + acute AMP. Long-term AMP-treatment comprised once daily i.p. injections of 5 mg/kg AMP for 14 consecutive days followed by 7 drug-free days. Acute AMP administration consisted of a single i.p. injection of 5 mg/kg. Acute AMP significantly increased the slope of the synaptic component, the excitatory postsynaptic potential (EPSP), of the evoked response without changing the cell discharge component (population spike), resulting in a significant decrease in the population spike per unit EPSP in the evoked potentials of both untreated and long-term AMP-treated rats. The acute AMP slightly reduced LTP of the population spike in the untreated rats and significantly reduced it in the long-term AMP-treated rats. LTP of the EPSP did not differ between the 4 conditions. The two saline conditions did not differ significantly in their evoked responses or in LTP. It is suggested that AMP has 3 acute effects in the dentate gyrus, and that the effect of reducing the capacity for LTP of the population spike is selectively enhanced following long-term AMP treatment.