Fig. 8.

Loss of ligand binding to dopamine receptors in HD mice. (A) Autoradiography experiments using [³H]-SCH1337, D1 receptor ligand and [³H]-spiperone, D2 receptor ligand, were performed in striata of BAC-225Q (n=4-12) and YAC128 animals (n=5–12). In BAC-225Q mice loss of ligand binding to D1 receptor is found at 6 months of age (^*t-test, p=0.002), and to D2 receptor - at 6 and 10 months of age (^*t-test, p<0.001; p=0.035, respectively). In YAC128 animals only loss of D2 ligand binding is observed (^*t-test, p=0.011; p=0.03, at 6 and 10 months respectively). (B) Dopamine receptor ligand binding in striatum was assessed also in spatiotemporal manner. In BAC-225Q mice, the impairment of either receptor is age- and subregion-dependent, starting from D1 ligand binding decrease at 3 months in caudal striatum (^*t-test, p=0.039), followed by loss of both receptor types at 6 months in all the three subdivisions (^*t-test, p=0.021; p<0.001; p=0.003 for D1, and p<0.001; p<0.001; p=0.006 for D2 in respectively, caudal, medial and rostral striatum), and finally D2 loss at 10 months in rostral striatum (^*t-test, p=0.014). In YAC128 animals the pattern of D2 receptor pathology appeared to be similar, but delayed compared to BAC-225Q mice. Loss of D2 ligand binding is observed at 6 months of age in caudal and medial striatum (^*t-test, p=0.024, p=0.022, respectively), and at 10 months in medial striatum (^*t-test, p=0.012). No changes in D2 receptor binding in rostral subdivision is found up to 10 months of age and no D1 pathology is observed in any part of striatum.