Sedative effects of the dopamine D1 receptor agonist A 68930 on rat open-field behavior

The present results demonstrate sedative effects of the DA D1 receptor agonist A 68930 (0.9-15 micromol kg(-1), s.c.) on rat spontaneous locomotor activity in an open field. The effects were particularly strong, and dose-dependent, for the ambulatory activity in the open-field arena (forward locomotion) and for rearing activity, whereas the suppression of locomotor activity (i.e. total horizontal activity in the open field) was less conspicuous. The distribution of activity within the open field (activity in center vs periphery) was not consistently affected by the A 68930 treatment. In support for DA D1 receptor mediated effects of A 68930, the effects on locomotor activity, forward locomotion, and on rearing behavior, were partially antagonized by the DA D1 receptor antagonist SCH 23390 (15 nmol kg(-1) s.c.). SCH 23390 by itself produced a modest, but statistically significant, suppression of these different items of open-field behavior. The atypical antipsychotic agent clozapine has previously, in this laboratory, been shown to stimulate DA D1 receptors in vivo. There are a number of clinical and laboratory observations, consistent with the notion of a beneficial role for such effects in schizophrenia. Thus, the sedation, apparently not related to extrapyramidal motor functions, produced by DA D1 receptor agonist A 68930 could reflect an important aspect of the mechanism of action for atypical antipsychotic drugs.