Changes at cholecystokinin receptors induced by long-term treatment with diazepam and haloperidol

Fourteen days administration of haloperidol (1 mg/kg daily) prevented the motor depressant effect of caerulein (an agonist at cholecystokinin receptors, 15 micrograms/kg) and the antagonistic effect of caerulein (100 micrograms/kg) against (+)-amphetamine (5 mg/kg) induced hyperlocomotion in mice. The antiaggressive effect of caerulein (40 micrograms/kg) in saline-treated mice was replaced by increased aggressiveness after long-term haloperidol and diazepam (5 mg/kg daily) treatment. The anticonvulsant effect of caerulein (125 micrograms/kg) against picrotoxin (10 mg/kg) induced seizures was abolished after 14 days diazepam, but not after haloperidol, treatment. The above described changes in the mouse behaviour are probably related to the development of subsensitivity at CCKA receptors, whereas the CCKB receptor subtype becomes more sensitized to the action of caerulein after long-term haloperidol and diazepam treatment.