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Psychopharmacology (Berl). 2009 Oct;206(3):415-27. doi: 10.1007/s00213-009-1620-6. Epub 2009 Aug 4.

Cognitive enhancing effects of ghrelin receptor agonists.

Author information

1
GlaxoSmithKline R&D China, Centre for Cognition and Neurodegeneration Research, Biopolis at One-North, 11 Biopolis Way, The Helios Building, #03-01/02, Singapore 138667, Singapore. Zeenat.I.Atcha@gsk.com

Abstract

RATIONALE:

Ghrelin, the endogenous ligand for the growth hormone secretagogue receptor, has been shown to play a role in multiple physiological processes including appetite regulation, metabolism and, more recently, dendritic spine architecture, long-term potentiation and cognition.

OBJECTIVE:

The objective of this study was to determine the effects of two structurally non-peptide ghrelin receptor agonists (GSK894490A and CP-464709-18) on rodent cognition.

METHODS:

All experiments were performed in male Lister hooded rats. Effects of the test compounds on rat cognitive performance was determined using the novel object recognition test, a modified water maze paradigm and a scopolamine-induced deficit in cued fear conditioning. These tests were chosen as they each probe a relatively independent cognitive domain and therefore potentially have differing underlying neural substrates.

RESULTS:

Both compounds significantly improved performance in the novel object recognition and modified water maze tests but were unable to attenuate a scopolamine deficit in cued fear conditioning.

CONCLUSIONS:

These results demonstrate that the small-molecule ghrelin receptor agonists profiled here readily cross the blood/brain barrier and elicit pro-cognitive effects in recognition and spatial learning and memory tests. Based on these observations, the central ghrelin receptor would appear to be a chemically tractable receptor and perhaps should be considered as a new drug target for therapeutic approaches to treat diseases affecting cognition.

PMID:
19652956
DOI:
10.1007/s00213-009-1620-6
[Indexed for MEDLINE]

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