The effects of
SKF 38393 (D1-agonist) and
SCH 23390 (D1-antagonist) were compared with those of
haloperidol (D2 greater than D1-antagonist) and
metoclopramide (D2-antagonist) in the absence or presence of
apomorphine (D1/D2-agonist) and
RU 24213 (D2 agonist) in non-habituated mice. The motor behaviour studied which was typical of the species included sniffing, grooming, rearing and locomotion.
Apomorphine and
RU 24213 induced frozen inactivity, in small doses and head-down sniffing, coupled with ponderous forward walking, in large doses, consistent with the stimulation of D2 receptors at pre- and postsynaptic sites, respectively. Neither
SKF 38393 nor
metoclopramide modified rearing or locomotion over a wide range of doses.
SKF 38393 promoted sniffing and grooming, while
metoclopramide suppressed this behaviour. Apart from increased grooming with
SCH 23390 in small doses, both this
drug and
haloperidol dose-dependently decreased all motor activity. In combination studies, the D2 blockers reversed the effects of stimulation of D2 receptors and released normal behaviour, whereas
SCH 23390 converted both the behavioural syndromes mediated by pre- and postsynaptic D2-receptors into severe inactivity (but not
catalepsy). The
drug SKF 38393 had the opposite effect and promoted motor responding in the presence of D2 stimulation, in doses that were otherwise ineffective by themselves. In this model,
SCH 23390 modified behaviour mediated by D2-receptors in a different manner to the D2-receptor antagonists,
haloperidol and
metoclopramide, suggesting it may interact with a different population of D2-receptors, or with D1-receptors. These and earlier data can be interpreted to mean that both subclasses of the
dopamine receptor have distinct and probably interdependent roles in the management of motor behaviour.