Alcohol Disinhibition of Behaviors in C. elegans

Abstract

Alcohol has a wide variety of effects on physiology and behavior. One of the most well-recognized behavioral effects is disinhibition, where behaviors that are normally suppressed are displayed following intoxication. A large body of evidence has shown that alcohol-induced disinhibition in humans affects attention, verbal, sexual, and locomotor behaviors. Similar behavioral disinhibition is also seen in many animal models of ethanol response, from invertebrates to mammals and primates. Here we describe several examples of disinhibition in the nematode C. elegans. The nematode displays distinct behavioral states associated with locomotion (crawling on land and swimming in water) that are mediated by dopamine. On land, animals crawl and feed freely, but these behaviors are inhibited in water. We found that additional behaviors, including a variety of escape responses are also inhibited in water. Whereas alcohol non-specifically impaired locomotion, feeding, and escape responses in worms on land, alcohol specifically disinhibited these behaviors in worms immersed in water. Loss of dopamine signaling relieved disinhibition of feeding behavior, while loss of the D1-like dopamine receptor DOP-4 impaired the ethanol-induced disinhibition of crawling. The powerful genetics and simple nervous system of C. elegans may help uncover conserved molecular mechanisms that underlie alcohol-induced disinhibition of behaviors in higher animals.

Mechanosensation circuitry in Caenorhabditis elegans: A focus on gentle touch

“…npr-1 mutants recover from ethanol exposure faster and exhibit higher levels of tolerance [19]. C. elegans failed to respond to nose touch when immersed in liquid, but treatment with ethanol restored nose touch responses [70]. This restoration of nose touch responses suggests that the circuitry mediating ethanol responses interacts with the nose touch pathway.…”

An Assay for Measuring the Effects of Ethanol on the Locomotion Speed of <em>Caenorhabditis elegans</em>

“…Interestingly, these diverse assays have yielded somewhat different dose response profiles for the effects of ethanol. These results have pointed to important differences in the underlying behaviors of crawling and swimming 9,23 , as well as a role for the environmental variable osmolarity in ethanol responses 20 , and have highlighted the importance of describing experimental detail of the various assays.…”

“…The nematode, Caenorhabditis elegans , has been increasingly used as a model for studying the effects of ethanol on behavior 7-9 . There is strong molecular conservation in the machinery of nervous system function between worms and mammals, and several genes that have been shown to influence the LR to ethanol in worms have been shown to influence LR to ethanol in mammals 10-16 , and have been implicated in abuse liability in humans 17-19 .…”

Conservation of the Ethanol-Induced Locomotor Stimulant Response among Arthropods

“…Bainton et al, 2000;Wolf et al, 2002], but not in another insect species, the honeybee Apis mellifera [Maze et al, 2006], or in the roundworm Caenorhabditis elegans [Mitchell et al, 2007; but see Topper et al, 2014]. It is possible that these results simply mirror the variation in the response seen among rodent strains, and that A. mellifera strains which do show a response could be found.…”