Cholecystokinin (CCK) and schizophrenia: the selective CCKB antagonist LY262691 decreases midbrain dopamine unit activity.
Chronic administration of antipsychotic drugs has previously been shown to decrease the number of spontaneously active midbrain dopamine cells. In an effort to evaluate CCK antagonists as potential antipsychotic drugs, we have examined the effects of a selective CCK-B antagonist, LY262691, on the number of spontaneously active midbrain dopamine neurons using extracellular, single-unit recordings in anesthetized rats. Acute and chronic administration of LY262691 decreased the number of spontaneously active A9 and A10 dopamine cells. Administration of apomorphine did not reverse the effect of LY262691 on A9 and A10 dopamine neurons. These results suggest that LY262691 may have an antipsychotic effect without delayed onset, and that its effects on dopamine cells may not be mediated through depolarization inactivation.
Eli Lilly & Co., Lilly Corporate Center, Indianapolis, IN 46285.
K
K
Rasmussen
M E
ME
Stockton
J F
JF
Czachura
J J
JJ
Howbert
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011720:Pyrazoles; D051381:Rats; D011919:Rats, Inbred Strains; D012559:Schizophrenia / Q000188:drug therapy*
D014150:Antipsychotic Agents; D011720:Pyrazoles; C074681:1-(4-bromophenylaminocarbonyl)-4,5-diphenyl-3-pyrazolidinone; D002766:Cholecystokinin; D001058:Apomorphine; D004298:Dopamine