REVERSAL OF STABLE BEHAVIORAL-MODIFICATIONS THROUGH NMDA RECEPTOR INHIBITION IN RATS

In order to study the effect of long-term dizocilpine infusion on memo ry, two different paradigms of stably modified behaviour were used in rats. The first was the escape deficits (ED) induced and maintained ei ther by repeated daily administrations of SKF 38393, a rather selectiv e D1 dopamine receptor agonist, or by repeated stress; the second was sensitisation to the effect of cocaine on motility. Fluoxetine (FLX), imipramine (IMI) and clomipramine (CMI) were equally effective in reve rsing the reduced reactivity of animals in both ED models, Dizocilpine showed a similar efficacy to that of classic antidepressants on the p harmacologically-induced ED, but failed to affect the stress-induced E D. In rats previously sensitised to cocaine and then infused with dizo cilpine for 7 days after suspension of cocaine administration, the sta te of sensitisation remained intact; however, in animals receiving diz ocilpine plus a concomitant daily injection of cocaine, dizocilpine si gnificantly reduced cocaine sensitisation. These results potentially s uggest a new approach to the treatment of drug addiction and other psy chiatric disorders. Finally, it was concluded that NMDA receptor block ade not only prevents, but also reverses many, if not all, learned beh aviours, and that this phenomenon differs from the effect of antidepre ssants.