Efficacy of the MCHR1 antagonist N-[3-(1-{[4-(3,4-difluorophenoxy)phenyl]methyl}(4-piperidyl))-4-methylphenyl]-2-methylpropanamide (SNAP 94847) in mouse models of anxiety and depression following acute and chronic administration is independent of hippocampal neurogenesis
被引:105
作者:
David, D. J.
论文数: 0引用数: 0
h-index: 0
机构:Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA
David, D. J.
Klemenhagen, K. C.
论文数: 0引用数: 0
h-index: 0
机构:Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA
Klemenhagen, K. C.
Holick, K. A.
论文数: 0引用数: 0
h-index: 0
机构:Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA
Holick, K. A.
Saxe, M. D.
论文数: 0引用数: 0
h-index: 0
机构:Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA
Saxe, M. D.
Mendez, I.
论文数: 0引用数: 0
h-index: 0
机构:Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA
Mendez, I.
Santarelli, L.
论文数: 0引用数: 0
h-index: 0
机构:Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA
Santarelli, L.
Craig, D. A.
论文数: 0引用数: 0
h-index: 0
机构:Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA
Craig, D. A.
Zhong, H.
论文数: 0引用数: 0
h-index: 0
机构:Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA
Zhong, H.
Swanson, C. J.
论文数: 0引用数: 0
h-index: 0
机构:Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA
Swanson, C. J.
Hegde, L. G.
论文数: 0引用数: 0
h-index: 0
机构:Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA
Hegde, L. G.
Ping, X. I.
论文数: 0引用数: 0
h-index: 0
机构:Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA
Ping, X. I.
Dong, D.
论文数: 0引用数: 0
h-index: 0
机构:Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA
Dong, D.
Marzabadi, M. R.
论文数: 0引用数: 0
h-index: 0
机构:Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA
Marzabadi, M. R.
Gerald, C. P.
论文数: 0引用数: 0
h-index: 0
机构:Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA
Gerald, C. P.
Hen, R.
论文数: 0引用数: 0
h-index: 0
机构:Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA
Hen, R.
机构:
[1] Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA
[2] Fac Pharm Chatenay Malabry, Neuropharmacol Lab, EA3544, Chatenay Malabry, France
Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that plays a role in the modulation of food intake and mood. In rodents, the actions of MCH are mediated via the MCHR1 receptor. The goal of this study was to investigate the effects of acute (1 h) and chronic (28 days) p.o. dosing of a novel MCHR1 antagonist, N-[3-(1-{[4-(3,4-difluorophenoxy)phenyl]methyl}(4-piperidyl))-4-methylphenyl]-2-methylpropanamide (SNAP94847), in three mouse models predictive of antidepressant/anxiolytic-like activity: novelty suppressed feeding (NSF) in 129S6/SvEvTac mice and light/dark paradigm (L/D) and forced swim test (FST) in BALB/cJ mice. A significant increase in the time spent in the light compartment of the L/D box was observed in response to acute and chronic treatment with SNAP 94847. An anxiolytic/antidepressant-like effect was found in the NSF test after acute and chronic treatment, whereas no effect was observed in the FST. Because neurogenesis in the dentate gyrus has been shown to be a requirement for the effects of antidepressants in the NSF test, we investigated whether neurogenesis was required for the effect of SNAP 94847. We showed that chronic treatment with SNAP 94847 stimulated proliferation of progenitors in the dentate gyrus. The efficacy of SNAP 94847 in the NSF test, however, was unaltered in mice in which neurogenesis was suppressed by X-irradiation. These results indicate that SNAP 94847 has a unique anxiolytic-like profile after both acute and chronic administration and that its mechanism of action is distinct from that of selective serotonin reuptake inhibitors and tricyclic antidepressants.