The effect of acute and chronic treatment with SCH 23390 on the spontaneous activity of midbrain dopamine neurons.

The effect of acute and chronic administration of SCH 23390 on the spontaneous activity of dopamine (DA) neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) was studied. Two groups of rats were given an acute subcutaneous (s.c.) injection of the specific D-1 DA receptor block SCH 23390 (0.5 or 1.0 mg/kg). In four separate chronic experiments, SCH 23390 was administered repeatedly for 21 days either s.c. (0.5 or 1 mg/kg) or orally (5 or 10 mg/kg). No change in the number of spontaneously active DA neurons was found either after acute or chronic treatment with SCH 23390. On the other hand, chronic (21 days) haloperidol (0.5 mg/kg per os) produced a marked reduction in the number of spontaneously active DA neurons both in the SNc and VTA, a finding previously shown to be due to the development of depolarization block. It is concluded that chronic D-1 DA receptor blockade, may not be involved in the development of depolarization block produced by chronic treatment with antipsychotic drugs.