THE NMDA ANTAGONIST DIZOCILPINE (MK801) ATTENUATES TOLERANCE TO NICOTINE IN RATS

The N-methyl-D-aspartate antagonist dizocilpine (MK801) has been shown to attenuate neuroadaptations of the locomotor activity responses see n after chronic nicotine administration in rats. The aim of the presen t study was primarily to examine the effects of dizocilpine on toleran ce to the aversive stimulus effect of nicotine, as measured in a condi tioned taste aversion (CTA) paradigm. A second aim was to determine wh ether the previously reported effect of dizocilpine on tolerance to th e locomotor depressant effect of nicotine could be confirmed. CTA was assessed from changes in the consumption of saccharin and salt solutio ns and locomotor activity was measured during 30 min sessions in photo cell cages. In control rats, the administration of nicotine (0.4 mg/kg s.c.) produced strong CTA and a biphasic effect on locomotor activity (depression followed by facilitation). Daily treatment for 7 days wit h nicotine (0.4 mg/kg s.c.) produced tolerance to the CTA and motor ef fects. This tolerance was not detectable in rats that had received diz ocilpine (0.3 mg/kg s.c.) 30 min before each daily injection of nicoti ne during the period of chronic treatment. The chronic administration of dizocilpine alone did not prevent locomotor effects and CTA when ni cotine was administered subsequently. These results suggest that the N MDA receptor may be involved in adaptation to both unconditioned and c onditioned behavioural responses to nicotine.