Effect of the selective dopamine D3 receptor antagonist SB-277011-A on regional c-Fos-like expression in rat forebrain

Abstract SB-277011-A is a dopamine D 3 receptor antagonist that exhibits over 100-fold selectivity over dopamine D 2 receptors and a broad spectrum of other receptor, ion channels, and enzymes. We employed c-Fos immunohistochemistry to characterise the functional neuroanatomical effects of acute administration of SB-277011-A and observed a time-dependent increase in the density of c-Fos-like positive nuclei in rat forebrain with maximal effects observed 2 h post-dose. The relative influence of the different brain regions on the overall effect of SB-277011-A was ranked by partial least squares discriminant analysis loadings plot which indicated that sites within the nucleus accumbens exerted the greatest influence on the separation of the vehicle and SB-277011-A treatment groups. At the 2 h time-point, c-Fos-like expression was shown to be significantly elevated ( p 3 receptor antagonism in psychiatric disorders including schizophrenia and drug dependency.