Journal Article

Emergence of anxiety-like behaviours in depressive-like <i>Cpe<sup>fat/fat</sup></i> mice

Ramona M. Rodriguiz, John J. Wilkins, Thomas K. Creson, Reeta Biswas, Iryna Berezniuk, Arun D. Fricker, Lloyd D. Fricker and William C. Wetsel

in International Journal of Neuropsychopharmacology

Published on behalf of International College of Neuropsychopharmacology

Volume 16, issue 7, pages 1623-1634
Published in print August 2013 | ISSN: 1461-1457
Published online August 2013 | e-ISSN: 1469-5111 | DOI:
Emergence of anxiety-like behaviours in depressive-like Cpefat/fat mice

Show Summary Details



Cpefat/fat mice have a point mutation in carboxypeptidase E (Cpe), an exopeptidase that removes C-terminal basic amino acids from intermediates to produce bioactive peptides. The mutation renders the enzyme inactive and unstable. The absence of Cpe activity in these mutants leads to abnormal processing of many peptides, with elevated levels of intermediates and greatly reduced levels of the mature peptides. Cpefat/fat mice develop obesity, diabetes and infertility in adulthood. We examined whether anxiety- and/or depressive-like behaviours are also present. Anxiety-like responses are not evident in young Cpefat/fat mice (∼60 d), but appear in older animals (>90 d). These behaviours are reversed by acute treatment with diazepam or fluoxetine. In contrast, increased immobilities in forced swim and tail suspension are evident in all age groups examined. These behaviours are reversed by acute administration of reboxetine. In comparison acute treatments with fluoxetine or bupropion are ineffective; however, immobility times are normalized with 2 wk treatment. These data demonstrate that Cpefat/fat mice display depressive-like responses aged ∼60 d, whereas anxiety-like behaviours emerge ∼1 month later. In tail suspension, the reboxetine findings show that noradrenergic actions of antidepressants are intact in Cpefat/fat mice. The ability of acute fluoxetine treatment to rescue anxiety-like while leaving depressive-like responses unaffected suggests that serotonin mechanisms underlying these behaviours are different. Since depressive-like responses in the Cpefat/fat mice are rescued by 2 wk, but not acute, treatment with fluoxetine or bupropion, these mice may serve as a useful model that resembles human depression.

Keywords: Anxiety; carboxypeptidase E; depression; encephalin convertase; neuropeptides; obesity

Journal Article.  7512 words.  Illustrated.

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.