Ay. Bespalov et al., Effects of the NMDA receptor antagonist, D-CPPene, on sensitization to theoperant decrement produced by naloxone in morphine-treated rats, BEHAV PHARM, 12(2), 2001, pp. 135-142
Sensitization to the rate-decreasing effects of opioid antagonists induced
by acute pretreatment with opioid agonists has been suggested to reflect in
itial changes in opioid systems that underlie physical dependence. Glutamat
e receptors are implicated in the development and expression of opioid depe
ndence, and antagonists acting at the N-methyl-D-aspartate (NMDA) subtype o
f glutamate receptors have been shown repeatedly to attenuate the severity
of opioid withdrawal, The present study evaluated the ability of a competit
ive NMDA receptor antagonist, D-CPPene (SDZ EAA 494; 3-(2-carboxypiperazin-
4-yl)-1-propenyl-1-phosphonic acid), to affect morphine-induced sensitizati
on to naloxone in rats trained to lever-press on a multiple-trial, fixed-ra
tio 10 schedule of food reinforcement, D-CPPene (0.3-3 mg/kg) was administe
red either 4 h or 30 min prior to the test session. Morphine (10 mg/kg) or
its vehicle was administered 4 h before naloxone challenge (0.3-3 mg/kg), D
-CPPene failed to prevent morphine-induced potentiation of the naloxone-pro
duced decrement in operant performance. Thus, these results suggest that ag
onist-induced sensitization to behavioral effects of opioid antagonists may
be insensitive to NMDA receptor blockade. (C) 2001 Lippincott Williams & W
ilkins.