Dopamine-receptor binding and adenylate-cyclase activity in mouse striatal tissue in the supersensitivity phase after neuroleptic treatment

The specific binding of ³H-labelled haloperidol (³H-Hal) and the basal and dopamine-stimulated adenylate-cyclase activity in vitro were investigated in mice treated with a single dose or with repeated doses of neuroleptic drugs. These dose regimens are known to induce behavioural supersensitivity and to decrease dopamine synthesis and release a few days after cessation of dosage.Shortly after a single dose of teflutixol (5 mg/kg i.p.) the binding of ³H-Hal was reduced to very low levels. Four and five days later the apparent number of receptor-binding sites was slightly reduced. The binding returned to normal levels after 6 days. The reduced binding most likely reflects the receptor blockade induced by teflutixol. Four days after treatment both basal and dopamine-stimulated adenylate cyclase were within normal limits. Six days following a single dose of piflutixol (0.08 mg/kg i.p.) a light increase in dopamine-stimulated adenylate cyclase activity was observed. Three days after repeated doses of haloperidol (1.25 mg/kg p.o. daily for 5 days), both basal and dopamine-stimulated adenylate cyclase were unchanged. After 3 weeks treatment with teflutixol (5 mg/kg i.p. daily), the specific binding of ³H-Hal was slightly reduced 5 days after, but almost equal to controls 8 days after the last dose.The data presented neither support nor reject the hypothesis of an increased number of DA receptors in the supersensitivity phase after neuroleptic treatment of mice.