Does neuroleptic blocking of dopamine receptors continue after chronic treatment?

Neuroleptic treatment of schizophrenia reduces CSF cyclic AMP in clinical responders after a mean of 8 weeks of treatment. This is consistent with continued effective dopamine receptor blockade by these drugs. Rat striatal 3H-spiroperidol binding sites increase more after 10 weeks of haloperidol therapy than after 3 weeks, suggesting that physiological equilibrium has not yet been reached by 3 weeks. The rat striatal receptor affinity for 3H-spiroperidol is decreased after 10 weeks but not after 3 weeks. The decreased affinity represents a new phenomenon that may be important in explaining long-term continuing neuroleptic effectiveness despite the increased receptor number. The decreased affinity of rat dopamine binding sites for 3H-spiroperidol after 10 weeks of neuroleptic treatment is consistent with the reduced human CSF cyclic AMP after a similar period of neuroleptic treatment.