EFFECTS OF ENVIRONMENTAL CONDITIONING ON THE DEVELOPMENT OF NICOTINE SENSITIZATION - BEHAVIORAL AND NEUROCHEMICAL ANALYSIS

We have investigated the effects of environmental conditioning on the induction of nicotine sensitization of locomotion, stereotypy and nucl eus accumbens dopamine release. Sprague-Dawley rats, some of which had been previously implanted with a microdialysis guide cannula over the nucleus accumbens, were sensitized with 5 days of repeated nicotine ( 0.6 mg/kg per day, SC) or saline injections (1 ml/kg per day). During nicotine treatment the drug administration was either paired with the microdialysis/activity monitor testing chamber (conditioned) (n=6) or with the animal's home cage (unconditioned) (n=6) and after 60 min the animal was returned to home cage and received a second injection of s aline 15 min later. A third group received saline in the testing appar atus followed by nicotine in the home cage (pseudo-conditioned) (n=6). In the guide cannulated animals, 2 mm microdialysis probes were inser ted after completing day 5 of treatment and all animals were tested fo r their response to nicotine (0.6 mg/kg, SC) on day 6. Both locomotor activity and nucleus accumbens dopamine release showed a larger respon se subsequent to nicotine challenge in the nicotine versus saline pret reated animals in the conditioned group, but not in the unconditioned group. In the pseudo-conditioned group there was an increase in the st ereotypy responses to nicotine, however the locomotor and dopamine rel ease responses were not significantly enhanced. The results from the c onditioned group were confirmed in animals which were tested for behav ioral activation and dopamine release simultaneously (n=5). These find ings indicate that nicotine sensitization of locomotor activity and nu cleus accumbens dopamine release (using a 5-day pretreatment protocol) is dependent on conditioning the animal to the testing environment du ring nicotine pretreatment.