Ea. Blokhina et al., Pretreatment with morphine potentiates naloxone-conditioned place aversionin mice: effects of NMDA receptor antagonists, EUR J PHARM, 406(2), 2000, pp. 227-232
Acute pretreatment with opioid receptor agonists potentiates behavioral eff
ects of opioid antagonists. This phenomenon was suggested to serve as an ac
ute model of opioid dependence. Since antagonists acting at N-methyI-D-aspa
rtate (NMDA) receptors were repeatedly shown to attenuate development, main
tenance, and expression of opioid dependence, the present study evaluated t
he effects of competitive NMDA receptor antagonist, D-CPPene (SDZ EAA 494;
3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid), and low-affinity
channel blocker, 1-amino-3,5-dimethyl adamantane hydrochloride (memantine)
, on establishment of naloxone-conditioned place aversion in mice that were
pre-exposed to morphine. Morphine (20 mg/kg) pretreatment significantly po
tentiated the ability of naloxone (0.01-0.3 mg/kg) to produce place aversio
n. The place aversion produced by naloxone (0.1 mg/kg) was attenuated by D-
CPPene (1 and 3 mg/kg but not 0.1 or 0.3 mg/kg) when it was administered 3.
5 h after morphine (0.5 h prior to conditioning trial with naloxone) but no
t 0.5 h prior to morphine. Memantine (1-10 mg/kg) had no effect under any t
reatment condition (0.5 h prior to morphine, simultaneously with morphine,
2 or 3.5 h after morphine). Thus, the ability of NMDA receptor antagonist t
o affect development and/or expression of morphine dependence may not be a
good predictor of their effects on establishment of morphine-potentiated na
loxone-conditioned place aversion. (C) 2000 Elsevier Science B.V. All right
s reserved.