545. A double-blind, placebo-controlled study of naltrexone in the treatment of pathological gambling disorder

Abstract

release of dopamine (DA) following the application of this alkaloid through a microdialysis probe placed in the striatum. We also measured the expression of mRNAs encoding for a3, a4, a7 and b2 nicotinic acetylcholine receptor (nAChR) subunits and, the density of high-affinity nAChRs in the striatum. The DA content in the dialysate was measured before and after 1-min local perfusion of nicotine (6, 10 and 20 nmoles/min) and the resulting DA increase was taken as a measure of the alkaloid’s intrinsic activity. The nicotine-induced increase of striatal DA release in FSL rats at all doses was greater than in the FRL rats. Mecamylamine, a non-competitive antagonist for nAChRs, attenuated nicotine-induced striatal dialysate DA increase to the same extent in both lines, suggesting that the intrinsic activity of nicotine was greater in the FSL rats than in the FRL rats. This suggestion was supported by the density of high-affinity nAChRs (measured by H-epibatidine binding) in FSL rats that was 44% greater than in the FRL rats while the KD was virtually identical in the two groups of rats. Also, the expression of mRNA encoding for a4, a7, and b2 subunits was greater in FSL than in FRL rats (attomol/mg total RNA, a4: 98.0 6 10.3 vs 77.3 6 7.4; a7: 278.8 6 16.3 vs 184 6 15.7; b2: 310.3 6 19.3 vs 200.8 6 11.6). We hypothesize that the differences in nicotine-induced DA release in striatum of FSL and FRL rats are probably associated with differences in nAChR subunit expression in the two lines. The Flinders rats could be used as animal model for nicotine self-administration studies to evaluate the sensitivity of FSL and FRL rats to nicotine dependence.