Calcium antagonists isradipine and nimodipine suppress cocaine and morphine intravenous self-administration in drug-naive mice.
The effect of isradipine and nimodipine, two dihydropyridine calcium antagonists, on intravenous self-administration of cocaine and morphine in naive mice has been investigated. When morphine or cocaine injections were made contingent upon nose-poke response by naive mice, they increased their rate of nose-poking with respect to animals receiving contingent saline injections or yoked control animals, receiving noncontingent cocaine or morphine injections. Pretreatment of mice with isradipine (1.0-3.0 mg/kg, SC) or nimodipine (5-20 mg/kg, SC) inhibited in a dose-related manner self-administration both of cocaine and morphine contingent upon a nose-poke response. The ED50 of isradipine against cocaine and morphine self-administration was 1.7 and 2.1 mg/kg, respectively. The relative values for nimodipine were 14.5 and 11.4 mg/kg, respectively. These data suggest that nimodipine and, especially, isradipine suppress the reinforcing properties of morphine and cocaine and may be an effective pharmacotherapy for treatment of cocaine and heroin abuse.
Kuzmin
A
A
Department of Pharmacology, Pavlov Medical Institute, St. Petersburg, Russia.
Zvartau
E
E
Gessa
G L
GL
Martellotta
M C
MC
Fratta
W
W
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage*; D004095:Dihydropyridines / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D007275:Injections, Intravenous; D017275:Isradipine; D051379:Mice; D009020:Morphine / Q000008:administration & dosage*; D009553:Nimodipine / Q000494:pharmacology*; D012054:Reinforcement, Psychology; D012201:Reward; D012646:Self Administration
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009553:Nimodipine; D009020:Morphine; D003042:Cocaine; D004298:Dopamine; D017275:Isradipine