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The central mechanism mediating the discriminative effects of nicotine was studied using rats. Rats were trained to discriminate subcutaneously administered nicotine at 0.5 mg/kg from saline in a 2-lever operant chamber situation for food reinforcement. 1) Nicotine administered into the lateral ventricle at both 100 micrograms and 120 micrograms substituted for subcutaneously administered nicotine at 0.5 mg/kg. This result indicates that the discriminative effects of nicotine are mediated centrally. 2) Among the drugs, acetylcholine at 0.5-10 micrograms administered into the lateral ventricle and methamphetamine at 5-40 micrograms and dopamine at 1-10 micrograms administered into the nucleus accumbens, none substituted for subcutaneously administered nicotine. These results indicate that the discriminative effects of nicotine differ from those of the above drugs. 3) Nicotine at 100 micrograms administered into the nucleus accumbens almost completely substituted for subcutaneously administered nicotine. In addition, mecamylamine at 180 micrograms administered into the nucleus accumbens attenuated the discriminative effects of subcutaneously administered nicotine. These results suggest that nicotinic receptors in the nucleus accumbens may be involved in the discriminative effects of nicotine. However, further studies are needed, since the nucleus accumbens is regarded not to be a major site of action of nicotine for these effects because of its low susceptibility to nicotine and mecamylamine.

Studies on the involvement of the nucleus accumbens in the discriminative effects of nicotine in rats.