Attenuation of the locomotor activating effects of D-amphetamine, cocaine, and scopolamine by potassium channel modulators.
1. Locomotor activating effects of D-amphetamine, cocaine, and scopolamine were determined alone and after pretreatment with K-channel modulators in mice. 2. When administered alone, D-amphetamine (1.0- 30 mg/kg) and cocaine (3.0- 56 mg/kg) produced inverted U-shaped dose-effect curves characteristic of psychomotor stimulant drugs. 3. When administered alone, scopolamine (3.0-56 mg/kg) also produced dose-dependent increases in locomotor activity but these effects plateaued with similar increases in locomotor activity induced by 10-56 mg/kg of scopolamine. 4. Pretreatment with the K-channel blockers 4-aminopyridine (0.3-1.7 mg/kg), quinine (30-100 mg/kg) or apamin (0.3-1.0 mg/kg) attenuated the locomotor increases induced by d-amphetamine, cocaine, and scopolamine. 5. Like the K-channel blockers, pretreatment with the K-channel openers cromakalim (1.0-3.0 mg/kg) and pinacidil (3.0-10 mg/kg) also attenuated the locomotor increases induced by D-amphetamine and scopolamine but did not modify the locomotor activating effects of cocaine. 6. These results demonstrate that K-channel modulation modifies the effects of D-amphetamine, cocaine, and scopolamine. 7. The results also demonstrate that K-channel openers can differentially alter the behavioral effects of cocaine and D-amphetamine.
Rosenzweig-Lipson
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S
CNS Disorders, Wyeth-Ayerst Research, Princeton, NJ, USA.
Thomas
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Barrett
J E
JE
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D019806:Cromakalim / Q000494:pharmacology; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D011803:Quinine / Q000494:pharmacology; D012601:Scopolamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D000697:Central Nervous System Stimulants; D018727:Muscarinic Antagonists; D015221:Potassium Channels; D019806:Cromakalim; D001030:Apamin; D011803:Quinine; D015761:4-Aminopyridine; D012601:Scopolamine; D003042:Cocaine; D003913:Dextroamphetamine