Functional supersensitivity of the hippocampal dopaminergic system after prolonged treatment with haloperidol

The effect of acute and prolonged (21 days) treatment with haloperidol (1 or 5 mg/kg SC) on the dopamine-, apomorphine- and LY 171555-induced changes in the firing rate of CA1 layer neurons was studied in a hippocampal slice preparation. Dopamine and apomorphine administration evoked either an excitatory or inhibitory reaction, while the selective D2 receptor agonist LY 171555 increased the firing rate of hippocampal neurons. The excitatory effects of dopamine and LY 171555 were blocked by sulpiride and haloperidol. Prolonged administration of haloperidol potentiated the excitatory reaction of dopamine and apomorphine; however, even a single dose of the neuroleptic enhanced the dopamine-induced effect. The reaction evoked by LY 171555 was not significantly affected by either acute or chronic treatment with haloperidol. The present findings indicate that long-term administration of haloperidol results in an increased sensitivity of hippocampal neurons to the mixed dopamine agonists, dopamine and apomorphine, but not to selective stimulation of the D2 receptor.