IDENTIFICATION OF AGE-RELATED-CHANGES OF DOPAMINE D-1-LIKE RECEPTORS IN THE RAT CEREBELLAR CORTEX

The present study was designed to characterize the pharmacological pro file of dopamine D-1-like receptors in the rat cerebellar cortex and t o assess if these receptor sites undergo age-related changes. Cerebell a of young (3 months), adult (12 months), and old (27 months) male Wis tar rats were examined by using radioligand binding techniques and lig ht microscope autoradiography. The non-selective dopamine D-1-like rad ioligand [H-3]SCH 23390 was specifically bound to sections of rat cere bellum. The findings that dopamine displaced [H-3]SCH 23390 binding in the submicromolar range suggest the labelling of a dopamine D-5 (or D -1B) receptor subtype. The affinity of [H-3]SCH 23390 for dopamine D-1 -like receptors was similar in the cerebellar cortex of the three anim al groups investigated, whereas radioligand binding techniques reveale d a gradual age-related reduction of the density of binding sites. Lig ht microscope autoradiography showed the localization of [H-3]SCH 2339 0 binding sites primarily in the molecular layer and to a lesser exten t in the Purkinje neuron layer of the cerebellar cortex. Aging was acc ompanied by a loss of [H-3]SCH 23390 binding sites affecting mainly th e molecular layer. The age-dependent loss of dopamine D-1-like recepto rs is more pronounced if detected with radioligand binding techniques than with light microscope autoradiography. This suggests that the dec rease of dopamine D-1-like receptors observed in aging rat cerebellar cortex may depend in part on changes in the receptor expression and in part on cortico-cerebellar structural changes. (C) 1995 Wiley-Liss, I nc.