Ia. Sukhotina et Ay. Bespalov, Effects of the NMDA receptor channel blockers memantine and MRZ 2/579 on morphine withdrawal-facilitated aggression in mice, PSYCHOPHAR, 149(4), 2000, pp. 345-350
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. Anta
gonists acting at the NMDA receptor are known to attenuate the expression o
f morphine withdrawal syndrome in laboratory animals. Objective: The presen
t study aimed to evaluate the effects of low-affinity NMDA receptor channel
blockers (memantine and MRZ 2/579) on aggression facilitated by morphine w
ithdrawal in mice. Methods: Significant increases in aggressive behavior we
re 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 intra
peritoneally 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 injecti
on. Results: Both compounds dose-dependently reduced the expression of aggr
essive behavior while having no significant effect upon the intensity of no
n-aggressive social contacts. Memantine significantly diminished the occurr
ence of all recorded components of aggressive behavior (attacks/bites, thre
ats, tail rattling) while MRZ 2/579 affected mainly the appetitive events o
f aggressive bursts (threats, tail rattling). For both compounds, anti-aggr
essive effects occurred at dose levels that did not produce motor impairmen
t 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 d
ue to specific interaction with morphine withdrawal-triggered processes.