Muscimol is a potent non-specific GABAAR agonist, a substrate for the GABA metabolizing enzyme GABA transaminase, metabolically unstable and a neurotoxin, and is therefore not suitable as a therapeutic compound. Nonetheless, it has been shown to possess some anxiolytic properties and has been used widely as a lead structure for new compounds that are potent and selective for the GABA-A receptors. So far, analogs of muscimol have been unsuitable for therapeutic purposes, due to adverse side effects.
SG-11-2-101 is a novel analog of muscimol and is hypothesized to possess similar anxiolytic properties. SG-11-2-101 has been tested in several behavioral tests predictive of anxiolytic action: elevated zero maze test, marble burying test, novelty-induced hypophagia test, and stress-induced hyperthermia test. In addition, side effects on spontaneous locomotor activity, motor coordination, and attention/working memory were assessed with the locomotor activity test, rotarod test and modified Y-maze test, respectively.
SG-11-2-101 showed anxiolytic-like effects in all tests of anxiolytic action and did not significantly affect behaviors in the side effect tests.
The purpose of this project is to prepare a manuscript for publication based on the behavioral results.
In this project, the research assistant will learn:
1) the role of GABA and its receptors in anxiety disorders
2) how to interpret results from mouse behavioral tests
3) how to write a manuscript for publication in a peer-reviewed scientific journal
Select Research Mentor bibliography:
- Refsgaard LK, Pickering DS, Andreasen JT. Investigation of antidepressant-like and anxiolytic-like actions and cognitive and motor side effects of four N-methyl-D-aspartate receptor antagonists in mice. Behav Pharmacol. 2017 Feb;28(1):37-47. doi: 10.1097/FBP.0000000000000266. PMID: 27740963
- Andreasen JT, Fitzpatrick CM, Larsen M, Skovgaard L, Nielsen SD, Clausen RP, Troelsen K, Pickering DS. Differential role of AMPA receptors in mouse tests of antidepressant and anxiolytic action.Brain Res. 2015 Mar 19;1601:117-26. doi: 10.1016/j.brainres.2015.01.001. Epub 2015 Jan 8.PMID: 25578259
- Nasser A, Møller LB, Olesen JH, Konradsen Refsgaard L, Andreasen JT. Anxiety- and depression-like phenotype of hph-1 mice deficient in tetrahydrobiopterin. Neurosci Res. 2014 Dec;89:44-53. doi: 10.1016/j.neures.2014.08.015. Epub 2014 Sep 10. PMID: 25218564
Related Discipline(s)
This course would also be of interest to the following discipline(s):Biomedicine / Biotechnology, Chemistry / Biochemistry
