Involvement of D2 dopamine receptors in the opposing effects of two CCK-B agonists in a spatial recognition memory task: role of the anterior nucleus accumbens.
BACKGROUND
A previous study in the rat has shown that systemic injection of two CCK-B agonists, BC264 and BC197, induced opposing effects on the retrieval phase of a spatial recognition memory task.


OBJECTIVE
The present study was designed to investigate the mechanisms underlying these effects at the level of the dopaminergic system.


METHODS
Rats were injected IPly with BC264 (0.3 microg/kg) or BC197 (30 microg/kg) and with D1 or D2 agonists and antagonists. The cognitive performances of rat were analysed on the retrieval phase of a spatial recognition memory task. The extracellular levels of dopamine were quantified in the anterior nucleus accumbens after injection of BC197 (3, 30 and 300 microg/kg IP), using the microdialysis technique on freely moving rats. Local injection of the D2 antagonist, sulpiride (2.5 ng/microl) was performed in the anterior nucleus accumbens and the cognitive performances analysed following systemic injection of BC264 (0.3 microg/kg).


RESULTS
The improvement and the impairment of performance induced respectively by BC264 and BC197 were suppressed by peripheral administration of sulpiride, showing that these opposing effects were both mediated by the stimulation of D2-like receptors. However, different dopaminergic pathways seem to be involved in the effects of the two CCK-B agonists. Indeed, systemic administration of BC197 did not induce the increase of extracellular dopamine levels observed with BC264. Furthermore, local injection of sulpiride, in the anterior nucleus accumbens, completely suppressed the cognitive enhancing effect of BC264.


CONCLUSIONS
These findings suggest that the D2-mediated deficit in the performance induced by BC197 involves brain structures other than the anterior nucleus accumbens. They also demonstrate a critical role of dopaminergic transmission within the anterior nucleus accumbens in the improving effect induced by BC264 in a spatial memory task.
Léna
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Département de Pharmacochimie Moléculaire et Structurale, INSERM U266, CNRS UMR 8600, UFR des Sciences Pharmaceutiques et Biologiques, Paris, France.
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D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D002766:Cholecystokinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004343:Drug Implants; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects*; D008845:Microinjections; D009714:Nucleus Accumbens / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000819:agonists*; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D013028:Space Perception / Q000187:drug effects*; D013238:Stereotaxic Techniques
D004343:Drug Implants; D010446:Peptide Fragments; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D017448:Receptors, Dopamine D2; D015102:3,4-Dihydroxyphenylacetic Acid; C060186:BC 197; D002766:Cholecystokinin; D004298:Dopamine; D006719:Homovanillic Acid