D2-like postsynaptic receptors are not functionally coupled to Gi/Go proteins in hMT mice. (a) DA-induced [35S]GTPγS binding was reduced in hMT mice. Striatal membranes of NT (n = 6), hWT (n = 6) and hMT (n = 6) mice were incubated with different concentrations of DA and 0.1 nM [35S]GTPγS for 90 min. Data are expressed as percent of [35S]GTPγS bound in the absence of DA and represent as mean ± SEM (n = 6). The dose–response curve from each animal was performed in duplicates. (b) Basal striatal D2R levels are reduced in hMT mice. Basal D2R expression levels in the striatum were determined by western blotting analysis in naïve NT (n = 25), hWT (n = 8) and hMT (n = 17) mice. (c) GRK2, GRK3, GRK6 and β-Arrestin2 content is unaltered in hMT mice (n = 8), compared to NT controls (n = 8). In contrast, RGS9 levels are significantly reduced in mutants (n = 16), compared to NT mice (n = 21). Upper panels in (b) and (c) show representative autoradiograms. The graphs show summary of values, normalized to DARPP32 and expressed as mean ± SEM. Genotypes are as indicated. * p < 0.05, ** p < 0.01, compared with NT mice.