Behavioral and neurochemical components of nicotine sensitization following 15-day pretreatment: studies on contextual conditioning.

The effects of contextual conditioning on the induction of nicotine sensitization of locomotor activity, stereotypy and nucleus accumbens dopamine release were studied using a 15-day pretreatment regimen. Six groups of Sprague-Dawley rats were employed to test for the effects of drug pretreatment, conditioning and novelty. Groups 1-4 were treated with daily nicotine (0.6 mg/kg, s.c.) or saline injections that were either paired with the test chamber or given in the home cage, followed by saline injections in the home cage. Group 5 received saline in the test chamber followed by nicotine in the home cage (unpaired). Group 6 was naive to handling and drug treatment. Pretreated animals were implanted with 2 mm microdialysis probes, via chronic guide cannulae, after completing the 15th day of treatment, and were tested for their response to nicotine (0.6 mg/kg, s.c) or saline on day 16. Naive animals were implanted with microdialysis probes and tested in a similar manner. Nicotine-stimulated locomotor activity was sensitized in the paired, unpaired and homecage pretreatment groups whereas nicotine-stimulated stereotypy was sensitized only in the paired pretreatment group. Nicotine-stimulated nucleus accumbens dopamine release was sensitized in the paired and unpaired pretreatment groups. Saline-stimulated nucleus accumbens dopamine release, but not locomotor activity or stereotypy, was also found in the nicotine-pretreated, paired group. These findings demonstrate the development of sensitization to nicotine-induced locomotor activity, stereotypy and nucleus accumbens dopamine release after a 15-day pretreatment regimen. Each of these responses to nicotine were differentially modulated by contextual conditioning. It is suggested that nicotine-stimulated dopamine release in sensitized animals represents the conditioned component of nicotine sensitization.