THE NMDA RECEPTOR ANTAGONIST MK-801 BLOCKS ACQUISITION AND EXTINCTIONOF CONDITIONED HYPOALGESIC RESPONSES IN THE RAT

The role of the N-methyl-D-aspartate (NMDA) receptor in Pavlovian cond itioning of hypoalgesic responses in the hotplate apparatus was examin ed using the non-competitive NMDA antagonist MK-801. Either MK-801 or saline were administered before the training phase, test phase, or bot h, and MK-801 disrupted the acquisition and extinction but not the exp ression of conditioned hypoalgesic responses. All rats received counte rbalanced injections of both MK-801 and saline after the training phas e, therefore the learning decrements could not be attributed to a dela yed, non-specific action of the drug. MK-801 did not augment paw-lick latencies on either the training or test days, indicating that its beh avioural effects are not due to alterations in nociceptive sensitivity or motor performance. Similarly, MK-801's effects upon acquisition an d extinction could not be attributed to state-dependent generalization decrement or impairments in processing of the hot-plate apparatus cue s during training, as rats displayed normal hypoalgesic responses when tested with MK-801, and MK-801-treated animals displayed normal habit uation of novelty-induced hypoalgesia in the hot-plate apparatus. Thes e data suggest that the NMDA receptor system is involved in the acquis ition and extinction, but not the expression of conditioned hypoalgesi a and parallels the effects of NMDA receptor antagonists on the acquis ition and expression of long-term potentiation (LTP) both in vitro and in vivo. It is plausible that an endogenous NMDA-mediated form of LTP plays a vital role in the acquisition and storage of aversive represe ntations mediating conditioned hypoalgesic responses.