The dopaminergic role of D-1 and D-2 receptors in
catalepsy was evaluated using drugs with preferential receptor affinities. The D-1 antagonist,
SCH 23390, caused distinct
catalepsy in mice at 1, 2, and 10 mg/kg, IP, but not at two lower doses. The selective D-1 blocker,
molindone, also caused
catalepsy at 5 and 10 mg/kg; and blockade of both receptor types produced additive cataleptogenic effects.
Apomorphine (4 mg/kg), which is an agonist for both receptors, potentiated SCH 23390-induced
catalepsy much more than it did the
catalepsy induced by
molindone; the potentiation was produced by higher, not lower, doses of
apomorphine. To determine if the
apomorphine potentiation was mediated by D-1 or D-2 receptors, we tested selective agonists in mice that were concurrently injected with selective blockers. SCH 23390-induced
catalepsy was potentiated by a large dose of the D-2 agonist,
bromocriptine. The
catalepsy of D-2 blockade with
molindone was not potentiated by the D-1 agonist,
SKF 38393, which slightly disrupted the
catalepsy of D-2 blockade. We conclude that
catalepsy is not a simple D-2 blockade phenomenon and that preferential antagonism of either receptor type can cause
catalepsy.
Catalepsy is most profound when both receptor types are blocked.
Dopamine agonists, in large concentrations, are known to promote movements, and thus it is not surprising that they tend to disrupt
catalepsy.(ABSTRACT TRUNCATED AT 250 WORDS)