Postsynaptic bimodal effect of sulpiride on locomotor activity induced by pergolide in catecholamine-depleted mice

In reserpinized (5 mg/kg, s.c.) mice treated with alpha-methyl-p-tyrosine (200 + 100 mg/kg, i.p.), increasing doses of the D-2 antagonist sulpiride had varying effects on locomotor activity induced by the mixed D-1/D-2 agonist pergolide (2 mg/kg, s.c.). Low doses of sulpiride (1 mg/kg, i.p.) significantly enhanced this activity whereas at higher doses (50 mg/kg) an inhibitory effect was observed. Amphetamine (3 mg/kg, i.p.) failed to reverse akinesia in this animal model, precluding the possibility of a presynaptically mediated phenomenon; in contrast, mice receiving reserpine alone showed a high degree of locomotor activity when challenged with amphetamine. The bimodal effect of sulpiride is thought to be mediated either by two different D-2 receptors located on the same cell or by the same receptor with different topographical localization on postsynaptic neurons mediating opposite functions.