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Amphetamine-Induced Dopaminergic Hypersensitivity in Guinea Pigs:  Implications in Psychosis and Human Movement Disorders

Harold L. Klawans, MD; David I. Margolin
Arch Gen Psychiatry. 1975;32(6):725-732. doi:10.1001/archpsyc.1975.01760240053004.
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Following chronic amphetamine pretreatment, guinea pigs demonstrate an increased sensitivity to both d-amphetamine sulfate- and apomorphine hydrochloride-induced stereotyped behavior. This observation suggests that chronic exposure to high doses of a dopamine agonist (d-amphetamine) alters the response of the brain to the subsequent administration of both indirect (d-amphetamine) and direct (apomorphine) dopamine agonists.

This altered response may be due to the development of dopamine receptor site hypersensitivity. Clinical evidence suggests that a similar agonist-induced hypersensitivity may play a role in the development of dyskinetic movement disorders and psychoses in humans following the chronic use of such dopamine agonists as amphetamine and levodopa.

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