The apomorphine-induced inhibition of dopaminergic neurons in the substantia nigra of the rat was significantly attenuated following 2 daily injections of 0.05, 0.5 or 2.0 mg/kg apomorphine for 5 consecutive days. In fact, many of these neurons responded with an increase in firing rate which was never observed in control animals. Neostriatal neurons, on the other hand, decreased their sensitivity to apomorphine only after long-term treatment with 0.5 or 2.0 mg/kg. Multiple injections of the low dose actually potentiated the apomorphine-induced inhibition in the neostriatum. These results, which are consistent with the differential sensitivity of dopaminergic and neostriatal neurons to acute apomorphine, suggest that the subsensitivity of pre- and postsynaptic dopamine receptors produced by long-term apomorphine treatment is dose-dependent.
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