Elevation of circulating prolactin concentrations may not cause striatal dopamine receptor supersensitivity

Neuroleptic drugs, on repeated administration, increase plasma prolactin levels and induce behavioural and biochemical changes suggesting supersensitivity of striatal dopamine receptors. It has been suggested that the increase in plasma prolactin is responsible for the change in striatal dopamine receptors. We now find that repeated administration of haloperidol (5 mg/kg i.p.) for 21 days, followed by a 3 day drug-washout period, caused a 12-fold increase in circulating prolactin concentration in samples taken 1 h after the last injection. Haloperidol treated animals also exhibited an exaggerated stereotyped response to apomorphine 0.0625-0.5 mg/kg s.c.) and an increase in striatal dopamine receptor numbers labelled by [3H]spiperone. Administration of the same dose of domperidone or sulpiride (5 mg/kg i.p., 21 days), compounds which penetrate poorly into brain, also elevated plasma prolactin levels, but failed to alter cerebral dopamine function. Our findings indicate that neuroleptic-induced elevations in plasma prolactin levels are not responsible for the induction of cerebral dopaminergic supersensitivity.