In humans, alcohol often alleviates anxiety and promotes social interactions, but it might also lead to risky or embarrassing behavior. (Yes, drunk dialers, hang your heads in shame.) This dishibitory effect of alcohol is not unique to humans: in Drosophila, alcohol disinhibits male-male courtship. Now Jon Pierce-Shimomura and his colleagues at the University of Texas, Austin have demonstrated that ethanol-induced disinhibition also occurs in C. elegans. Their results appear in the journal PLoS ONE (1).
“We started this alcohol disinhibition story because it’s a behavioral response that we frequently experience with drinking alcohol, and people still don’t exactly know how it works at the molecular level,” noted Pierce-Shimomura.
When immersed in liquid, C. elegans normally suppress several behaviors typically observed on land, including foraging, spontaneous and touch-induced reversals in direction, and escaping from blue light. In addition, crawling (with an S-shaped body posture) is inhibited in favor of swimming (with a C-shaped posture). But give that same worm some alcohol, and everything changes.
“Just put the worms in [500mM ethanol], and as they’re experiencing the drug, they’ll go into bouts of inappropriate behaviors that they normally would never show in liquid. That’s the worm version of disinhibition,” explained Pierce-Shimomura. All of the land-based behaviors reappeared in worms immersed in ethanol.
In other animal models, the dopaminergic neural pathway plays a key role in ethanol-induced disinhibition. Worms deficient in dopamine signaling due to the disruption of dopamine synthesis or the deletion of dopamine receptors showed reduced disinhibition of foraging behavior. Interestingly, the levels of disinhibition for reversals and escape from blue light were not affected, strongly suggesting that a non-dopaminergic pathway is involved for these two behaviors.
Pierce-Shimomura previously demonstrated that the dopaminergic system is also involved in the transition from swimming to crawling in C. elegans, and it appears to play a role in the disinhibition of crawling since this disinhibition was reduced in worms lacking D1-like dopamine receptors. However, mutant worms deficient in dopamine synthesis did not show the same reduction in crawl disinhibition, suggesting that ethanol was acting directly through a specific D1-like dopamine receptor or a downstream pathway. This result was unexpected since previous studies attributed the link between ethanol-induced disinhibition and dopamine receptors to increased dopamine levels seen after intoxication.
Pierce-Shimomura plans to focus his future work on the novel observation that ethanol directly interacts with dopamine receptors. “I’d really like to find the molecules that are involved with this in the downstream pathways,” he said.
Given that the disinhibited behaviors of the worm don’t even remotely approach the alcohol-fueled debauchery seen during college spring break, one may wonder if there are in fact any social or sexual behaviors in C. elegans where disinhibition could be studied. “There might be some examples already that we haven’t appreciated in the past. C. elegans can be a social animal.” While he has no plans to study this himself, perhaps this would make a good project for a (sober) college student—after spring break, that is.
1. Topper S.M., S.C. Aguilar, V.Y. Topper, E. Elbel, and J.T. Pierce-Shimomura. 2014. Alcohol Disinhibition of Behaviors in C. elegans. PLoS ONE 9(3): e92965. doi:10.1371/journal.pone.0092965