Rationale: Individuals vary in sensitivity to the behavioral effects of nicotine, resulting in differences in vulnerability to nicotine addiction. The role of rearing environment in determining individual sensitivity to nicotine is unclear. The neuropharmacological mechanisms mediating the effect of rearing environment on the behavioral actions of nicotine are also poorly understood. Objectives: The contribution of rearing environment in determining the sensitivity to the interoceptive effects of nicotine was determined in rats reared in isolated conditions (IC) or enriched conditions (EC). The role of dopamine receptors and α4β2*-nicotinic acetylcholine (nACh) receptors in mediating the differential effect of IC and EC on the interoceptive action of nicotine was determined. Methods: The interoceptive action of nicotine was measured as the discriminative stimulus effect of nicotine. Mecamylamine- and eticlopride-inhibition of the nicotine stimulus were used to examine nACh and dopamine receptors, respectively. α4β2*-nACh receptor expression in the mesolimbic dopamine pathway was determined by quantitative autoradiography of [ 125 I]-epibatidine binding. Results: EC-reared rats are less sensitive than IC-reared rats to the discriminative stimulus effects of nicotine at all but maximally effective doses. Mecamylamine inhibited the nicotine stimulus threefold more potently in EC-reared rats (IC 50 = 0.25 mg/kg) compared to IC-reared rats (IC 50 = 0.75 mg/kg); eticlopride inhibition was not different. [ 125 I]-epibatidine binding in the ventral tegmental area of EC-reared rats was reduced (2.8 ± 0.3 fmol) compared to that of IC-reared rats (4.0 ± 0.4 fmol); there was no difference in the nucleus accumbens. Conclusions: Rearing environment regulates the sensitivity to the interoceptive effects of nicotine and α4β2*-nACh receptor expression in the mesolimbic dopamine pathway.
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