Many environmental changes impact sleep, such as exposure to drugs, social isolation, and varying temperatures. We are subjecting a wild-derived panel of flies to four different psychotropic drugs. This panel of lines, the Drosophila Genetic Research Panel (DGRP), is fully sequenced and polymorphisms both within and among these lines are known.
Aim 1. We generated a dose response curve for lithium chloride, LiCl. We based the nominal drug dosage for the flies on the usual dosage given to humans, corrected for body weight. Using a subset of DGRP lines with long and short-sleeping phenotypes, we tested the viability of the flies after chronic exposure to LiCl and determined the Lethal Dose 50% (LD50). From these curves we chose an appropriate dosage at which to measure the entire DGRP population.
Aim 2. We are currently measuring sleep in the DGRP in flies exposed to dosage of LiCl determined in Aim 1. We will then perform a genome-wide association study on the effects of drug exposure on sleep and compare it to sleep under normal conditions. We will identify those gene networks that are robust across environments, and those gene networks that are plastic and perhaps unique to each environment.
Aim 3. Little is known about the pharmacokinetics and molecular pharmacology of LiCl in flies. We will therefore quantify the concentrations LiCl in the body of each fly, and relate these measurements to the observed effect on sleep.