Your epilepsy research group has received reports from physician colleagues in the Michigan
Medicine Department of Neurology that a less-commonly prescribed antidepressant (GLH) may
have anticonvulsant effects in patients with epilepsy. A search of the primary research literature
available in NCBI PubMed provides you with some preliminary, although incomplete,
information:
- It is widely thought, though unconfirmed, that GLH’s activity is mediated through its
effects on serotonergic neurotransmission. - Patients typically lost a moderate amount of weight while they were taking the drug.
You plan to generate data about the mechanism of action of GLH and its efficacy as an
anticonvulsant in the hopes of repurposing this drug for seizure control.
Available tools: (you may describe others; you do not need to use all of these)
Mice with genetic deletions of specific 5-HT2 receptor subtypes, or of other proteins
such as SERT.
Mice experiencing spontaneous seizures due to mutations (such as Scn1a+/- mice).
Zebrafish which exhibit spontaneous epileptiform activity (Scn1Lab or scn1a fish)
Unmodified (wild type) mice and rats.
5-HT2 Agonists: Ag-AC (2A/2C), Ag-A (2A), Ag-B (2B), Ag-C (2C), Ag-BC (2B/2C), PanAg (nonspecific = agonist to any 5-HT2 receptor).
5-HT2 Antagonists: Ant-AC (2A/2C), Ant-A (2A), Ant-B (2B), Ant-C (2C), Ant-AB (2A/2B),
Ant-BC (2B/2C).
SERT antagonist: Fluoxetine.
Serotonin releasing agent: Fenfluramine.
Drugs to induce in vivo seizures or in vitro epileptiform activity.
Equipment or other necessary reagents to perform any experiment we have discussed in
this module.
For each experiment in each question below, your answer must include:
Experimental design (5 points): Identify what type of experiment you have selected
(microdialysis, fish field potentials, etc.), the model you will use (in vitro, animal model, etc.), and
how your chosen experiment will answer the question/test the hypothesis.
Variables (5 points): Describe all independent variables that you will be manipulating
(conditions, drug treatment, concentrations, etc). Identify your positive and negative control(s).
Data (5 points): Assume that your hypothesis is correct. Describe the results, in detail, that you
would predict. You may describe this in text or include a simple example figure.