Dizocilpine-like discriminative stimulus effects of low-affinity uncompetitive NMDA antagonists.
Neuropharmacology January 1, 1996 K A Grant, G Colombo, J Grant et al.
In rats trained to recognize the drug dizocilpine, various NMDA receptor antagonists were tested for their ability to produce similar effects. The dissociative anesthetics dizocilpine, phencyclidine, and ketamine fully substituted for dizocilpine without slowing response rates. Dexoxadrol also fully substituted but reduced response rates by 35%. Memantine, a low-affinity antagonist, fully substituted but only at doses that reduced response rates by 68%. Other low-affinity antagonists showed partial or no substitution, often at rate-reducing doses. The findings indicate that low-affinity NMDA antagonists produce discriminative stimulus effects distinct from those of dissociative anesthetics, with only the more potent low-affinity drugs showing substantial substitution, and then only at doses that impair behavior.