Cholecystokinin antagonist lorglumide reverses chronic haloperidol-induced effects on dopamine neurons.
Intravenous administration of the cholecystokinin (CCK) antagonist lorglumide (LORG) reversed chronic haloperidol (CHAL)-induced depolarization inactivation (DI) of dopamine (DA) cells in both the A9 and A10 areas. Moreover, microinjection of LORG, but not naloxone, directly into the medial nucleus accumbens (mNAc) dose-dependently reversed CHAL-induced effect. LORG injected into other brain regions was without effect. These results suggest that CCK receptors in the mNAc form an important link for maintaining CHAL-induced DI of DA cells and that CCK is involved in the therapeutic action of antipsychotic drugs.
Jiang
L H
LH
Department of Psychiatry and Behavioral Sciences, State University of New York, Stony Brook 11794-8790.
Kasser
R J
RJ
Wang
R Y
RY
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D005973:Glutamine / Q000031:analogs & derivatives*; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012686:Septal Nuclei / Q000502:physiology*; D012844:Sincalide / Q000378:metabolism / Q000502:physiology*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D005973:Glutamine; D011377:Proglumide; D006220:Haloperidol; C048181:lorglumide; D012844:Sincalide; D004298:Dopamine