Analgesic and reinforcing effects of morphine in mice. Influence of Bay K-8644 and nimodipine.
The aim of the present work was to clarify the role of calcium influx through L-type calcium channels in the rewarding and analgesic effects of morphine. Therefore the effects of Bay K-8644 and nimodipine, dihydropyridine calcium agonist and antagonist, respectively, on the analgesic and rewarding effects of morphine in mice were studied. Morphine-induced analgesia was measured with the aid of writhing test, hot plate test and tail clip test. The rewarding properties of morphine were studied using i.v. self-administration in drug-naive mice. Bay K-8644 potentiated morphine-induced analgesia in all the tests. The influence of nimodipine on morphine analgesia was more complicated and depended on the dose of morphine and test used. In self-administration experiments morphine exhibited the bell-shaped concentration-response curve. Bay K-8644 produced a shift of the curve to the left, while nimodipine had the opposite action indicating, respectively, facilitating and inhibitory influence on morphine rewarding effect. It is concluded that nimodipine exhibits partial antagonistic properties towards the rewarding action of morphine and slightly potentiates morphine-induced analgesia while Bay K-8644 increases either the rewarding or the analgesic effects of morphine.
Kuzmin
A V
AV
Department of Pharmacology, Pavlov Medical, Institute, St. Petersburg, Russia.
Patkina
N A
NA
Zvartau
E E
EE
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009553:Nimodipine / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010147:Pain Measurement / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D012054:Reinforcement, Psychology; D012646:Self Administration
D000700:Analgesics; D009553:Nimodipine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009020:Morphine; D002118:Calcium