The ability of drugs, selective for
dopamine D1 and D2 receptors, to influence the production of
motor seizures was studied in mice and rats. Mice, which had been injected with
reserpine (5 mg/kg) to deplete stores of monoamines in brain, could be made to convulse 24 hr later by injecting the D1 agonists,
SKF 38393 (15-30 mg/kg) and
CY 208-243 (0.3-3 mg/kg). The D2 agonists,
lisuride (0.5-5 mg/kg) and
RU 24213 (0.5-15 mg/kg) and the mixed D1/D2 agonist,
apomorphine (0.05-0.5 mg/kg), had no effect on the seizure thresholds by themselves. However, the proconvulsant action of
SKF 38393, 15 mg/kg, was prevented by the simultaneous injection of
lisuride (5 mg/kg),
RU 24213 (5 mg/kg) or
apomorphine (0.5 mg/kg) and also by the selective D1 blocking
drug,
SCH 23390 (0.1 mg/kg). Rats were made to convulse by injecting the
cholinergic agonist,
pilocarpine (200-600 mg/kg) coupled with methyl
scopolamine (1 mg/kg), to prevent peripheral
autonomic effects. The smallest dose of
pilocarpine (200 mg/kg) was subconvulsant, whereas the larger ones (400 and 600 mg/kg) dose-dependently induced tonic convulsions. The
drug SKF 38393 (30 mg/kg) was found to be proconvulsant and caused
seizures to develop in 100% of animals, at all dose levels of
pilocarpine. This effect was blocked by
SCH 23390 (0.25 mg/kg) which, by itself, reduced the severity and increased the latency of
pilocarpine-induced convulsions, but not their frequency. The D2 agonist
LY 171555 (0.5 mg/kg) was also
anticonvulsant in this model and was antagonised by the D2 blocking
drug metoclopramide (1.25 mg/kg), which was ineffective alone.