Genetic and pharmacological analysis of neurotransmitters controlling egg laying in C. elegans.
We have investigated the neurotransmitters used to control egg-laying in C. elegans. Previous studies suggested that 5-HT released by the HSN motor neurons stimulates egg laying, and that tricyclic antidepressants potentiate egg laying by blocking reuptake of 5-HT by the HSN neurons. We report studies of the wild type and a mutant that lacks detectable 5-HT that suggest 5-HT is not required for egg-laying. Furthermore, we find that ACh is required for egg laying in response to 5-HT, suggesting that 5-HT is not sufficient to activate egg laying. The dominant egl-2(n693) mutation, which causes animals to lay eggs in response to tricyclics but not 5-HT, also conflicts with the model for egg laying. Experiments in which the HSN neurons or 5-HT are removed from egl-2 animals indicate that the action of tricyclics cannot be explained by a block of 5-HT reuptake. We find that D2 family dopamine antagonists can also induce egg laying in egl-2(n693) mutants, and that dopamine inhibits egg laying in the wild type. These results suggest that dominant egl-2 mutations activate an inhibitory dopaminergic pathway that can be blocked by tricyclics and D2 antagonists. We also find that these drugs stimulate egg laying in mutants lacking 5-HT or the HSN neurons, consistent with a target on the egg-laying muscles. In contrast to tricyclics, fluoxetine and other selective 5-HT reuptake inhibitors appear to be specific for 5-HT reuptake in C. elegans egg laying.
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D017173:Caenorhabditis elegans / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D005821:Genetic Techniques; D007422:Intestines / Q000294:innervation; D009130:Muscle, Smooth / Q000294:innervation; D009154:Mutation; D009433:Neural Inhibition; D009474:Neurons / Q000502:physiology; D018377:Neurotransmitter Agents / Q000502:physiology*; D010058:Oviposition / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000235:genetics / Q000502:physiology
D000929:Antidepressive Agents, Tricyclic; D018492:Dopamine Antagonists; D018377:Neurotransmitter Agents; D005473:Fluoxetine; D012701:Serotonin; D000109:Acetylcholine