UNDER CONTINUOUS DIZOCILPINE INFUSION AN N-METHYL-D-ASPARTATE RECEPTOR-INDEPENDENT FORM OF COCAINE SENSITIZATION DEVELOPS IN RATS

N-methyl-D-aspartate (NMDA) receptor blockade is thought to prevent th e development of cocaine-induced sensitization. Moreover, when cocaine is administered daily along with dizocilpine infusion to previously s ensitized rats, the extinction of sensitization occurs. We report here two sets of experiments: (1) Rats were infused with dizocilpine throu gh a subcutaneous mini-pump (0.1 mg/kg/day) during the induction of co caine sensitization and, after 2 or 7 days of wash-out, were challenge d with: cocaine, dizocilpine plus cocaine or ((+/-)2-carboxypiperazin- 4-yl)-propyl-L-phosphonic acid (CPP) plus cocaine. Cocaine induced ste reotypy scores significantly lower than that produced by the two drug combinations. Animals infused with dizocilpine alone did not present s tereotypies when challenged either with dizocilpine or with dizocilpin e plus cocaine. (2) Rats previously sensitized to cocaine received diz ocilpine by infusion and daily cocaine treatments for a week. During t he first days of infusion, sensitization appeared to be significantly decreased, but it resumed the initial intensity on days 6 7. After 2 a nd 9 days of wash-out, the expression of sensitization could be retrie ved only by dizocilpine plus cocaine. Two distinct forms of sensitizat ion to cocaine thus seem to exist: one dependent on and the second ind ependent of NMDA receptor activity.