Amphetamine-induced dopaminergic hypersensitivity in guinea pigs. Implications in psychosis and human movement disorders.
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.
D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage / Q000494:pharmacology; D001519:Behavior / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D018492:Dopamine Antagonists; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006801:Humans; D007980:Levodopa / Q000009:adverse effects; D009069:Movement Disorders / Q000139:chemically induced*; D011605:Psychoses, Substance-Induced / Q000209:etiology*; D011930:Reaction Time / Q000187:drug effects; D011955:Receptors, Drug; D012559:Schizophrenia / Q000139:chemically induced / Q000503:physiopathology; D013239:Stereotyped Behavior / Q000187:drug effects*; D019966:Substance-Related Disorders / Q000150:complications
D018492:Dopamine Antagonists; D011955:Receptors, Drug; D007980:Levodopa; D000661:Amphetamine; D001058:Apomorphine