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procedure but did not ch<strong>an</strong>ge <strong>the</strong> corticosterone response. Moreover, whereas chronic exposure<br />

to daily footshock stress reduced c-Fos expression in <strong>the</strong> dentate gyrus of <strong>the</strong> hippocampus,<br />

agomelatine treatment reversed this effect <strong>an</strong>d normalized neuronal activity to basal levels. Also,<br />

chronic agomelatine led to increased hippocampal cell proliferation (Ki-67 labeling) <strong>an</strong>d survival<br />

(BrdU labeling) in stressed but not in control rats. Fur<strong>the</strong>rmore, agomelatine treatment reversed<br />

<strong>the</strong> stress-induced decrease in <strong>the</strong> number of doublecortin-positive neurons. Taken toge<strong>the</strong>r,<br />

<strong>the</strong>se data show that agomelatine counteracts <strong>the</strong> deleterious effects of stress on <strong>the</strong> brain by<br />

restoring stress-affected neuronal activation <strong>an</strong>d promoting hippocampal neurogenesis, which is<br />

in line with <strong>the</strong> previous findings in <strong>an</strong>imal models of depression (4,5).<br />

(1) B<strong>an</strong>asr et al., Biol Psychiatry 2006, 59:1087-1096.<br />

(2) Conboy et al., Int J Neuropsychopharmacol <strong>2009</strong>, 12:329-341.<br />

(3) Trent<strong>an</strong>i et al., Neurobiol Dis 2003, 14:602-618.<br />

(4) Maccari et al., Am Soc Neurosci, 2005, 566.8.<br />

(5) Païz<strong>an</strong>is et al., Eur Neuropsychopharmacol 2008, 18 (1), S316.<br />

Disclosures: G. Dagyte, None; E.A. V<strong>an</strong> der Zee, None; P. Meerlo, None; F. Postema,<br />

None; A. Trent<strong>an</strong>i, None; C. Gabriel, None; E. Mocaer, None; P.G.M. Luiten, None; J.A.<br />

Den Boer, None.<br />

Poster<br />

549. Mood Disorders: Experimental Therapeutics <strong>an</strong>d Novel Compounds<br />

Location: South Hall A<br />

Time: Tuesday, October 20, <strong>2009</strong>, 8:00 am - 12:00 noon<br />

Program#/Poster#: 549.4/W36<br />

Topic: C.16.f. Mood disorders: Experimental <strong>the</strong>rapeutics, preclinical studies<br />

Title: Exendin-4 stimulates hippocampal neurogenesis <strong>an</strong>d exerts affective <strong>an</strong>d cognition<br />

associated effects in behavioral models<br />

Authors: O. ZACHRISSON, R. ISACSON, E. NIELSEN, G. BERTILSSON, K. DANNAEUS,<br />

*L. B. WIKSTROM;<br />

NeuroNova AB, Stockholm, Sweden<br />

Abstract: Neurogenesis in <strong>the</strong> adult hippocampus plays a central role in key aspects of<br />

hippocampal functioning. The glucagon-like peptide 1 receptor agonist exendin-4 (Ex-4) has<br />

been shown to stimulate neurogenesis in <strong>the</strong> SVZ/medial striatum as previously shown<br />

(Bertilsson et al, J Neurosci Res, 2008). The aim of this study was to assess <strong>the</strong> effect of Ex-4<br />

treatment in rodents on hippocampal neurogenesis, <strong>an</strong>d on mood <strong>an</strong>d cognition associated<br />

behavior. Ex-4 is used clinically (Byetta) to treat diabetes type II <strong>an</strong>d displays gluco-

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