Induced Mutation in Caenorhabditis elegans Causes Dopamine Resistance

Abstract

In humans, drug addiction is linked to varying dependencies of dopamine levels in the brain. The neurotransmitter is involved in many behavioral mechanisms in animals and mediates the reward pathway. In C. elegans, one of the effects of dopamine is to inhibit motor neuron activity and create a basal slowing response in the N2 (wild types). As a result, egg-laying in wild types is inhibited. To induce egg laying, mutagenized C. elegans were created with EMS (ethyl methansulfonate) to potentially produce a dopamine resistant mutation. After mutagenesis, 334 nematodes were isolated and screened for egg laying behavior. Both wild type and mutant nematodes were exposed to M9 (control), dopamine, and L-dopa (dopamine precursor) solutions. After 1 hour of incubation in these conditions, quantitative analysis was performed to assess the amount of eggs produced. Using an ANOVA test, statistical significance (p<0.001) was found between the wild type and mutant groups both exposed to dopamine. This implies there has been an induced dopamine resistance. The precursor to dopamine, L-dopa, showed similar effects with regard to egg laying behavior. When the dopamine pathway in C. elegans is known, the gene or group of genes implicated for dopamine resistance can be determined. Once identified, a homologous gene in humans could be located and studied for similar drug-resistant effects. The knowledge gained from this research has implications in the fields of gene therapy and drug abuse.