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Effect of chronic amphetamine exposure on stereotyped behavior: implications for pathogenesis of l-dopa-induced dyskinesias.

The effect of chronic high doses of d-amphetamine on amphetamine- and apomorphine-induced stereotyped behavior in guinea pigs was studied in an attempt to determine the mechanism involved in the development of L-DOPA-induced dyskinesias in parkinsonism. Prolonged pretreatment with suprathreshold doses of amphetamine decreased the threshold dosage of both amphetamine and apomorphine necessary to elicit stereotyped behavior. This suggests that chronic striatal dopamine stimulation may induce striatal dopamine receptor site hypersensitivity and that this type of induced hypersensitivity may play a role in the development of L-DOPA-induced dyskinesia. This mechanism may also play a role in the development of amphetamine-induced chorea and psychosis.