K-channel blockers attenuate the presynaptic effects of the D2/D3 agonist quinpirole in monkeys.
The present study investigated whether potassium channel blockade could modify the behavioral effects of the dopamine D2/D3 receptor agonist quinpirole in squirrel monkeys. The duration of immobility and/or unusual postures indicative of catalepsy-associated behavior or the duration of scratching, known to be related to the effects of low and high doses, respectively, of quinpirole, were scored during 5-min observation periods in three squirrel monkeys. Saline or incremental doses of quinpirole were administered 10 min before each observation period. Administration of saline did not increase the durations of catalepsy-associated behavior (8% of the observational period) or scratching (< 1% of the observational period). Low doses of quinpirole (0.003-0.03 mg/kg) dose dependently increased the duration of catalepsy-associated behavior to approximately 54% of the observational periods. Higher doses of quinpirole (0.1-0.3 mg/kg) did not increase the duration of catalepsy; rather, these doses increased the duration of scratching to approximately 57% of the observational periods. The differential induction of catalepsy-associated behavior or scratching is believed to be related to, respectively, pre- and postsynaptic activity of quinpirole on dopamine D2/D3 receptors. Pretreatment with the potassium channel blockers apamin, 4-aminopyridine, and amodiaquin attenuated the effects of quinpirole (0.03 mg/kg) on catalepsy-associated behavior, with cataleptic postures maintained for 27, 21, and 24% of the observational periods, respectively. In contrast, pretreatment with potassium channel blockers did not consistently affect the scratching induced by quinpirole. In addition, apamin did not attenuate the catalepsy-associated behavior induced by the postsynaptic D2 receptor antagonist haloperidol (0.01-0.1 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
Rosenzweig-Lipson
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Lederle Laboratories, American Cyanamid Company, Pearl River, NY 10965, USA.
Barrett
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JE
D015761:4-Aminopyridine / Q000494:pharmacology; D000655:Amodiaquine / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D002375:Catalepsy / Q000139:chemically induced / Q000503:physiopathology; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D015221:Potassium Channels / Q000187:drug effects*; D019257:Quinpirole; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3; D017661:Receptors, Presynaptic / Q000187:drug effects; D012453:Saimiri
D018491:Dopamine Agonists; D004873:Ergolines; D015221:Potassium Channels; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D017661:Receptors, Presynaptic; D019257:Quinpirole; D000655:Amodiaquine; D001030:Apamin; D015761:4-Aminopyridine; D006220:Haloperidol