ACTION SEQUENCING IS IMPAIRED IN D-1A-DEFICIENT MUTANT MICE

The role of dopamine in the production of behaviour is multifarious in that it can influence different aspects of movement (e.g. movement in itiation, sensorimotor integration, and movement sequencing). A charac teristic of the dopamine system which seems to be critical for the exp ression of this diverse influence is its varied receptor population. P revious studies have shown that specific receptor subtype activation l eads to specific behavioural responses or alterations of selective asp ects of movement. It is known that one of the important influences of dopamine includes sequential co-ordination of 'syntactic' patterns of grooming movements because moderate loss of the dopaminergic nigrostri atal projections specifically disrupts these patterns without affectin g grooming actions in a general fashion (Berridge, K.C. Psychobiology, 15, 336, 1989). The specific receptors of the dopamine family which p lay a key part in this co-ordination of movement sequences is not know n. In the present study, we examined the serial order of particular sy ntactic sequences or chains of grooming actions in mice lacking D-1A r eceptors to explore the relationship between this receptor subtype and movement sequencing. Mutant mice had shorter grooming bouts and a dis ruption of the organization of sequential patterns compared with wild- type littermate controls. Sequential disruption was reflected in the f ailure of D-1A mutants to follow the syntactic pattern of grooming to completion. This sequential disruption deficit appeared to be specific , as mutant mice initiated more syntactic chains than wild-type contro ls even though they were less likely to complete them. These results s upport the hypothesis that D-1A receptor activation plays a part in th e sequencing of natural action. This conclusion has important implicat ions for the understanding of the functional heterogeneity of dopamine receptor subtypes and of the aetiology of symptoms observed in patien ts with basal ganglia disease.