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.
Highlights
Ethanol (EtOH) is the most commonly abused drug, in part because of its culturally condoned role in disinhibiting behaviors that are suppressed during states of anxiety
We examined whether EtOH induces disinhibition in the model nematode Caenorhabditis elegans and if the dopaminergic system was implicated in these effects
This includes social, sexual, and locomotor behaviors [1,2,3,4,5,8,9]. Such disinhibition has been demonstrated in fly and rodent models [10,11,12,18,30]. This disinhibition was shown to be reliant on the D1 class of dopamine receptors in flies and rodents
Summary
Ethanol (EtOH) is the most commonly abused drug, in part because of its culturally condoned role in disinhibiting behaviors that are suppressed during states of anxiety. While the phenomenon of disinhibition by EtOH in humans has been known for some time, studying the neural mechanisms underlying these behaviors relied upon the development of appropriate animal models. EtOH disinhibits locomotor patterns, often measured through the transient increase in total movement during acute intoxication as well as grooming [10,11,12]. Animals exposed to isolation stress displayed anxiety behaviors, assessed as reduced entries and time spent in the open arm in an elevated plus-maze test, which were partially relived by EtOH intoxication [13,14]. We examined whether EtOH induces disinhibition in the model nematode Caenorhabditis elegans and if the dopaminergic system was implicated in these effects. Disinhibition of several of these behaviors was reliant on dopamine signaling
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