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→Rx Probing Anesthetic-Receptor Interactions
*Would flumazenil block propofol's effect on the GABA<sub>A</sub>R, despite binding at a different site? What to make of the off-target effects?
*Would flumazenil block propofol's effect on the GABA<sub>A</sub>R, despite binding at a different site? What to make of the off-target effects?
*'''When given together with "promiscuous" anesthetics, what happens? For instance, is propofol equally effective when given with a specific HCN1 receptor inhibitor? What about a GABA<sub>A</sub>R inhibitor?'''
*'''When given together with "promiscuous" anesthetics, what happens? For instance, is propofol equally effective when given with a specific HCN1 receptor inhibitor? What about a GABA<sub>A</sub>R inhibitor?'''
*''C. elegans'' drug screen
**We do a screen where we feed the animals different drugs that act on the same receptors as a typical anesthetic, but that highly selective modulators of those receptors, for an hour, then bathe them in the anesthetic of interest and look for differences in the EC50 or in the behavior.
**''C. elegans'' has strong cuticle that decreases absorption of lots of drugs. May have to make them eat the drug before hand instead of just bathing them in it. He doesn't know if there's a way to predict which drugs cross the cuticle or validate that a drug in fact made it across.
**Swimming assay (easiest) or crawling assay
**Should be able to build a simple behavioral rig for less than $200
**Recommends '''connecting with [https://bioscience.utah.edu/faculty/maricq/index.php Andrew Maricq]''' at UofU who is a worm researcher interested in learning, memory, synapse formation, and neural circuits. He may be able to help get me started with ''C. elegans'' research or collaborate on setting up a screen.
**Hamilton is going to start thinking about how to record behavior from multiple wells at once, or how to automate serial well acquisition.
**I should start by making agar, isolating and plating E.coli colonies, picking worms, mastering worm husbandry, and acquiring images of WT behaviors.
**Hamilton is doing a screen of ketamine and isoflurane and trying to get genetic lines to test the relevant receptors.
====Genetic Probing of Anesthetic-Receptor Interactions====
====Genetic Probing of Anesthetic-Receptor Interactions====