Morphine Tolerance and Dependence in Mice with History of Repeated Exposures to NMDA Receptor Channel Blockers

Mice were subjected to two successive treatment protocols: first with NMDA receptor channel blockers (14 days, once a day) and second with morphine (5 mg/kg, 8 days, once a day). Treatment with the higher doses of dizocilpine (1 mg/kg), memantine (30 mg/kg), and MRZ 2/576 (30 mg/kg) upon discontinua...

Full description

Saved in:
Bibliographic Details
Published inPharmacology, biochemistry and behavior Vol. 63; no. 4; pp. 613 - 619
Main Authors Dravolina, Olga A, Belozertseva, Irina V, Sukhotina, Irina A, Bespalov, Anton Y
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.08.1999
Subjects
Analgesia
Analgesics, Opioid - pharmacology
Animals
Cyclopentanes - pharmacology
Dependence
Dizocilpine
Dizocilpine Maleate - pharmacology
Drug Tolerance
Excitatory Amino Acid Antagonists - pharmacology
Interpersonal Relations
Male
Memantine
Memantine - pharmacology
Mice
Morphine
Morphine - pharmacology
Morphine Dependence - psychology
MRZ 2/579
Reaction Time - drug effects
Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors
Social interaction test
Tolerance
Analgesia
Memantine
Dizocilpine
Social interaction test
MRZ 2/579
Dependence
Tolerance
Morphine
Mice
Online AccessGet full text

Cover

More Information
Summary:Mice were subjected to two successive treatment protocols: first with NMDA receptor channel blockers (14 days, once a day) and second with morphine (5 mg/kg, 8 days, once a day). Treatment with the higher doses of dizocilpine (1 mg/kg), memantine (30 mg/kg), and MRZ 2/576 (30 mg/kg) upon discontinuation revealed only minor behavioral abnormalities attributable to the state of withdrawal. Following repeated administration of low-dose morphine, tolerance to morphine analgesia developed in mice preexposed to dizocilpine (1 mg/kg but not 0.3 mg/kg) but not memantine (10 and 30 mg/kg), MRZ 2/579 (10 and 30 mg/kg), or saline. There were no signs of morphine dependence in any treatment group. Overall, the present study found only minor effects of the subchronic administration of high doses of NMDA receptor channel blockers, suggesting that clinical use of NMDA receptor channel blockers such as memantine will not be accompanied by increased propensity to induction of morphine tolerance and dependence.
ISSN:0091-3057
1873-5177
DOI:10.1016/S0091-3057(99)00028-3