Changes in the behavioral and biochemical effects of cerulein, an analog of cholecystokinin octapeptide, after prolonged administration of haloperidol

In experiments on male mice and rats, long-term haloperidol administration (0.25 mg/kg twice a day during 15 days) significantly changed behavioural effects of caerulein, an agonist of CCK-8 receptors. As a rule, the effects of caerulein were reduced or inverted; only long-term antagonism with amphetamine motor excitation in rats increased after the cessation of haloperidol administration. The decrease or inversion of caerulein's effects was connected with reduction of high-affinity dopamine2- and low-affinity CCK-8 receptors' density, reflecting the inhibition of some interneurons' activity in subcortical forebrain structures after haloperidol treatment. A more pronounced inhibition of dopamine's release by caerulein was the reason for the increased antiamphetamine action after long-term haloperidol treatment. It seems possible that both above mechanisms are involved in the antipsychotic action of haloperidol.