Cholecystokinin tetrapeptide improves water maze performance of neonatally 6-hydroxydopamine-lesioned young rats.
This study addressed the proposed memory-modulating effect of the cholecystokinin (CCK) 2 agonist Boc-CCK-4 in rats using a Morris water maze. In the brain, CCK is colocalized and interacts with dopamine, respectively. To impair dopaminergic neurotransmission, and consequently, dopamine-mediated learning and memory, rat pups received the neurotoxin 6-hydroxydopamine (6-OHDA) into the left [Day 5 postnatal (p.n.)] and right (Day 8 p.n.) ventricles (50 microg/5 microl each). After 6-OHDA treatment, dopamine brain levels were reduced by 60% on Day 50 p.n. Lesioned rats had a lower body weight but normal swimming abilities. In the acquisition phase of the water maze (Day 50 p.n.), sham-lesioned rats learned quickly, compared to lesioned rats. Treatment with Boc-CCK-4 (40 microg/kg ip) did not affect performance in sham-lesioned rats but restored the learning curve in lesioned rats without increasing swimming speed indicating a better spatial learning in the dopamine-depleted rats. In summary, these findings demonstrate that stimulation of CCK2 receptors may counteract cognitive deficits of dopamine-depleted rats.
Rex
André
A
Institute of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universität Berlin, Koserstr. 20, D-14195 Berlin, Germany. andrerex@zedat.fu-berlin.de
Fink
Heidrun
H
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006948:Hyperkinesis / Q000139:chemically induced / Q000523:psychology; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine; D011247:Pregnancy; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000819:agonists; D013550:Swimming / Q000502:physiology; D013563:Sympathectomy, Chemical; D013758:Tetragastrin / Q000494:pharmacology*
D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; D016627:Oxidopamine; D004298:Dopamine