Identification of age-related changes of dopamine D1-like receptors in the rat cerebellar cortex.

Abstract

The present study was designed to characterize the pharmacological profile of dopamine D1-like receptors in the rat cerebellar cortex and to assess if these receptor sites undergo age-related changes. Cerebella of young (3 months), adult (12 months), and old (27 months) male Wistar rats were examined by using radioligand binding techniques and light microscope autoradiography. The non-selective dopamine D1-like radioligand [3H]SCH 23390 was specifically bound to sections of rat cerebellum. The findings that dopamine displaced [3H]SCH 23390 binding in the submicromolar range suggest that labelling of a dopamine D5 (or D1B) receptor subtype. The affinity of [3H]SCH 23390 for dopamine D1-like receptors was similar in the cerebellar cortex of the three animal groups investigated, whereas radioligand binding techniques revealed a gradual age-related reduction of the density of binding sites. Light microscope autoradiography showed the localization of [3H]SCH 23390 binding sites primarily in the molecular layer and to a lesser extent in the Purkinje neuron layer of the cerebellar cortex. Aging was accompanied by a loss of [3H]SCH 23390 binding sites affecting mainly the molecular layer. The age-dependent loss of dopamine D1-like receptors is more pronounced if detected with radioligand binding techniques than with light microscope autoradiography. This suggests that the decrease of dopamine D1-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.