The Role Of The Dopamine/Ecdysteroid Receptor Dopecr In Ethanol Induced Behavioral Disinhibition

Ethanol, a main active ingredient of alcoholic beverages, exerts numerous effects on behavior through its interaction with diverse membrane and signaling molecules and effector cells. The effects include lack of motor control, behavioral disinhibition, tolerance, sensitization and addiction. In particular, behavioral disinhibition is typically associated with heavy drinking and can lead to detrimental consequences such as car accidents, violent rages, risky sexual behavior and illegal substance abuse. This research aimed to clarify the neural elements and cellular mechanisms underlying behavioral disinhibition induced by ethanol. The neurotransmitter dopamine (DA) is implicated in ethanol-induced behavioral disinhibition (Van Gaalen et al., 2006). To better understand the mechanism that DA regulates ethanol-associated behavioral disinhibition, my study focused on the D1-like receptor DopEcR, an insect G-protein coupled receptor that binds to both DA and steroid hormone ecdysone, in the fruit fly Drosophila melanogaster. Drosophila melanogaster is a useful model organism to study the genetic and neural mechanisms underlying ethanol consumption, abuse and addiction (Kaun et al., 2011). The fly brain is anatomically simple yet mediates many of the same behaviors observed in intoxicated humans (Kong et al., 2010). Wild type flies show disinhibited inter-male courtship, a type of cognitive behavioral disinhibition, under the influence of ethanol and behavioral sensitization to this behavior with recurring ethanol exposures (Lee et al., 2008). We found that DopEcR deficient (der) male flies show abnormal disinhibited courtship and sensitization as well as altered synaptic molecule expression upon recurrent ethanol exposures. The der mutantâ??s courtship phenotype was fully restored by expressing DopEcR during adulthood. This indicates a physiological (DopEcR functions at the time of ethanol exposure), rather than developmental, role of DopEcR for courtship disinhibition and sensitization. In addition, the der mutantâ??s abnormal courtship disinhibition was fully rescued by reinstating DopEcR expression in the mushroom body (MB) neurons, indicating the important role of the MB DopEcR in ethanol induced behavioral plasticity. Our study uncovers a key in vivo function for the novel G-Protein coupled DA/ecdysone receptor in ethanol-associated behaviors