Rats of Flinders Sensitive (FSL) and Flinders Resistant lines (FRL) differ in their susceptibility to physiological and associated behavioral responses elicited by
nicotine. In the present study, we measured
dopamine (DA) content in striatal
dialysates to investigate the sensitivity of FSL and FRL rats to
nicotine delivered locally through a microdialysis probe placed in the striatum. We also measured the expression density of striatal high-affinity
nicotinic acetylcholine receptors (nAChRs), and that of mRNAs encoding for alpha3, alpha4, alpha7 and beta2 nAChR subunits in both lines. The DA content of
dialysates was measured before and after a 1-min perfusion of
nicotine (6, 10 or 20 nmoles/min) and the resulting DA increase was taken as a measure of the
alkaloid's intrinsic activity for nAChRs involved in the release of DA. The
nicotine-induced increase of striatal DA release was greater in FSL than in FRL rats for all concentrations of
nicotine, suggesting that the intrinsic activity of
nicotine was greater in the FSL than in the FRL rats. This was further supported by our finding that the density of high-affinity nAChRs in the striatum of FSL rats was 44% greater than in the FRL rats, whereas affinity (K(D)) was virtually the same in the two lines of rats. Also the expression of mRNAs encoding for alpha(4), alpha(7), and beta(2) subunits in the striatum was greater in FSL than in FRL rats (attomol/microg total
RNA, alpha(4):98+/-10 vs. 77+/-7; alpha(7):279+/-16 vs. 184+/-16; beta(2):310+/-19 vs. 201+/-12). We hypothesize that the difference in
nicotine-induced DA release in the striatum of FSL and FRL rats depends on the difference in nAChR subunit expression in the striatum between the two lines. The Flinders rats could be used as a model for
nicotine self-administration studies to evaluate the susceptibilities of FSL and FRL rats to
nicotine dependence.