Cholecystokinin knock-down in the basolateral amygdala has anxiolytic and antidepressant-like effects in mice.
Fiche publication
Date publication
août 2012
Journal
Neuroscience
Auteurs
Membres identifiés du Cancéropôle Est :
Mme KOEBEL Pascale, Dr LUTZ Pierre-Eric
Tous les auteurs :
Del Boca C, Lutz PE, Le Merrer J, Koebel P, Kieffer BL
Lien Pubmed
Résumé
Cholecystokinin (CCK) is a neuropeptide widely distributed in the mammalian brain. This peptide regulates many physiological functions and behaviors, such as cardio-respiratory control, thermoregulation, nociception, feeding, memory processes and motivational responses, and plays a prominent role in emotional responses including anxiety and depression. CCK-expressing brain regions involved in these functions remain unclear and their identification represents an important step towards understanding CCK function in the brain. The basolateral amygdala (BLA) is strongly involved in emotional processing and expresses high levels of CCK. In this study we examined the contribution of CCK expressed in this brain region to emotional responses in mice. To knockdown CCK specifically in the BLA, we used stereotaxic delivery of recombinant adeno-associated viral vectors expressing a CCK-targeted shRNA. This procedure efficiently reduced CCK levels locally. shCCK-treated animals showed reduced levels of anxiety in the elevated plus-maze, and lower despair-like behavior in the forced swim test. Our data demonstrate that CCK expressed in the BLA represents a key brain substrate for anxiogenic and depressant effects of the peptide. The study also suggests that elevated amygdalar CCK could contribute to panic and major depressive disorders that have been associated with CCK dysfunction in humans.
Mots clés
Amygdala, metabolism, Animals, Anxiety, metabolism, Cholecystokinin, deficiency, Depression, metabolism, Gene Knockdown Techniques, Image Processing, Computer-Assisted, In Situ Hybridization, Male, Mice, Mice, Inbred C57BL, Reverse Transcriptase Polymerase Chain Reaction
Référence
Neuroscience. 2012 Aug 30;218:185-95