Effects of the NMDA receptor channel blockers memantine and MRZ 2/579 on morphine withdrawal-facilitated aggression in mice |
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Authors: | I A Sukhotina A Y Bespalov |
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Institution: | (1) Laboratory of Behavioral Pharmacology, Institute of Pharmacology, Pavlov Medical University, 6/8 Lev Tolstoy St., St. Petersburg 197089, Russia e-mail: abespalov@spmu.rssi.ru, Fax: +7-812-346-3414, RU |
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Abstract: | Rationale: Opioid withdrawal is known to facilitate aggressive behavior in laboratory rodents. Aggression develops as the somatic signs
disappear and thus may reflect protracted withdrawal-related behavioral alterations. Antagonists acting at the NMDA receptor
are known to attenuate the expression of morphine withdrawal syndrome in laboratory animals. Objective: The present study aimed to evaluate the effects of low-affinity NMDA receptor channel blockers (memantine and MRZ 2/579)
on aggression facilitated by morphine withdrawal in mice. Methods: Significant increases in aggressive behavior were observed 48 h after repeated morphine administration (8 days, b.i.d.,
10–80 mg/kg, SC) was discontinued. Separate groups of mice were treated intraperitoneally with vehicles or different doses
of memantine (1, 3, 10 or 30 mg/kg) or MRZ 2/579 (1, 3 or 10 mg/kg) 48 h after the last morphine injection. Results: Both compounds dose-dependently reduced the expression of aggressive behavior while having no significant effect upon the
intensity of non-aggressive social contacts. Memantine significantly diminished the occurrence of all recorded components
of aggressive behavior (attacks/bites, threats, tail rattling) while MRZ 2/579 affected mainly the appetitive events of aggressive
bursts (threats, tail rattling). For both compounds, anti-aggressive effects occurred at dose levels that did not produce
motor impairment in the Rotarod test. Conclusions: Taken together with the evidence on the lack of selective anti-aggressive effects of these drugs in morphine-naive mice,
attenuation of the aggression observed in the present study may be due to specific interaction with morphine withdrawal-triggered
processes.
Received: 2 May 1999 / Final version: 17 November 1999 |
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Keywords: | Aggressive behavior Resident-intruder test Rotarod test NMDA receptor channel blocker Opioid withdrawal Mice |
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