Abstract
Dopamine is a mediator of the stimulant properties of drugs of abuse, including ethanol, in mammals and in the fruit fly Drosophila. The neural substrates for the stimulant actions of ethanol in flies are not known. We show that a subset of dopamine neurons and their targets, through the action of the D1-like dopamine receptor DopR, promote locomotor activation in response to acute ethanol exposure. A bilateral pair of dopaminergic neurons in the fly brain mediates the enhanced locomotor activity induced by ethanol exposure, and promotes locomotion when directly activated. These neurons project to the central complex ellipsoid body, a structure implicated in regulating motor behaviors. Ellipsoid body neurons are required for ethanol-induced locomotor activity and they express DopR. Elimination of DopR blunts the locomotor activating effects of ethanol, and this behavior can be restored by selective expression of DopR in the ellipsoid body. These data tie the activity of defined dopamine neurons to D1-like DopR-expressing neurons to form a neural circuit that governs acute responding to ethanol.
Highlights
Alcoholism is a major societal problem with great medical, financial and social costs
For low to moderate doses of ethanol, DA signaling is associated with euphoria, locomotor activation, and drug seeking
Our studies extend the understanding of the role of DA in ethanol responses in flies in three main ways
Summary
Alcoholism is a major societal problem with great medical, financial and social costs. Environmental and genetic factors contribute to the susceptibility to alcoholism, and it is well established that the initial sensitivity of an individual to ethanol correlates with the likelihood of developing alcohol use disorders [1]. Breeding studies in rodents have identified positive correlations between the locomotor stimulant properties of acute ethanol exposure, a measure of ethanol sensitivity, and its reinforcing properties, suggesting that a genetic link for these traits may be evolutionarily conserved [2,3]. Acute and repeated exposure to ethanol as well as to most other abused drugs increases dopamine (DA) levels in the mesolimbic region of the brain [4]; this brain region mediates many aspects of drug responding and reinforcement in a wide variety of behavioral paradigms [5]. Definition of the molecular, cellular, and neural circuit effects of acute ethanol exposure can provide a mechanistic understanding of how ethanol co-opts normal brain functions, and a foundation for understanding the complex shifts in behavior and physiology that underlie the development of addiction
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
