Pretreatment with morphine potentiates naloxone-conditioned place aversionin mice: effects of NMDA receptor antagonists

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.