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Research Assistant: In Vivo Effects of the GABAA Agonist and Muscimol Analog SG-11-2-101 in Mice

Introduction to the topic:

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.

Project details:

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

Selected relevant publications:

  • 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

Prerequisites

One year of biology and one year of biochemistry at university level.

Additional application required

You must submit an additional application through the Online Registration portal.

All application materials must be submitted on the following dates by midnight in your time zone:

  • November 1 for spring semester applicants
  • May 1 for fall semester applicants

Complete your application through Student Registration.

Faculty

Jesper T. Andreasen

Faculty

Ph.D. (Psychopharmacology, University of Copenhagen, 2009). M.Sc. (Psychopharmacology, University of Copenhagen, 2004). Post-doctoral fellow at the Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen. With DIS since 2012.

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