title: Microinjection of cholecystokinin into the rat ventral tegmental area potentiates dopamine-induced hypolocomotion.
abstract: Cholecystokinin, (CCK) 1-400 ng, significantly potentiated the hypolocomotion induced by dopamine, when simultaneously microinjected bilaterally into the ventral tegmental area (VTA) of rat brain. Within this dose range, CCK had no effect alone on ambulatory locomotion. Topographical analysis indicated that the modulatory effect of CCK was greatest in the central and caudal regions of the VTA, and absent at sites lateral, dorsal, rostral, and caudal to the VTA. Pharmacological analysis indicated that both unsulfated CCK octapeptide (100 ng) and the C-terminal tetrapeptide of CCK (400 ng) potentiated dopamine-induced hypolocomotion in a manner identical with sulfated CCK octapeptide (100 ng). Proglumide, an antagonist of the peripheral-type CCK receptor, did not block the potentiating actions of CCK, at doses of proglumide up to 500 mg/kg i.p., or 100 micrograms into the ventral tegmental area. L-364,718, an antagonist of the peripheral-type CCK receptor with lesser affinity for the central-type CCK receptor, blocked the potentiating actions of CCK at relatively high doses of L-364,718 (1-10 mg/kg i.p.). These findings suggest that CCK acts as a facilitatory modulator of dopamine at a central-type CCK receptor on the A10 cell bodies.
authors.affiliation: Clinical Neuroscience Branch, National Institute of Mental Health, Bethesda, Maryland 20892.
authors.forename: J N
authors.initials: JN
authors.lastname: Crawley
mesh_terms: D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012844:Sincalide / Q000494:pharmacology; D013681:Tegmentum Mesencephali / Q000187:drug effects / Q000502:physiology*
chemical_list: D002766:Cholecystokinin; D012844:Sincalide; D004298:Dopamine