The role of D1/dDA1 and D5/DAMB dopamine receptors in ethanol induced behavioral disinhibition
Alcohol drinking causes changes in behaviors by acting on various neurotransmitters (e.g. GABA, acetyl choline and glutamate) (Kumar et al., 2009), neuromodulators (e.g. dopamine, and serotonin) (Banerjee, 2014) and ion channels (e.g. Ca2+ and K channels) (Harris and Hood, 1980). Behaviors associated with alcohol consumption include loss of motor coordination, impaired decision-making, altered circadian rhythm, and disinhibited behaviors (NIH-NIAAA, Bethesda, MD). Behavioral disinhibition is defined as having poor judgment and acting in a manner that one would not usually behave (Greenspan and Ferveur, 2000) and commonly caused by substance abuse such as alcohol consumption and cocaine use. Excessive alcohol intake can also have detrimental impacts such as car accidents leading to death, violent attacks, and unsafe sexual behaviors. Furthermore, alcohol consumption affects the sleep cycle (Sharma et al., 2017), which could aggravate behavioral disinhibition. This research aims to identify the mechanism by which ethanol induces behavioral disinhibition. Drosophila melanogaster was used as a model organism for this study. Drosophila and mammals have similar behavioral responses to ethanol (Kong et al., 2010). Wild-type flies exhibit disinhibited inter-male courtship under the influence of ethanol and the level of disinhibited courtship increases with recurring ethanol exposure (Lee et al., 2008), which represents behavioral sensitization (Berger et al., 2004). Behavioral sensitization is an enhanced response to stimulus after multiple exposures and underlies drug addiction (Walker, 1999). Dopamine is a major neuromodulator in both flies and mammals and plays roles in reward, attention, learning, memory, motivation, sleep, and ethanol-induced disinhibition Oishi and Lazarus, 2017; van Gaalen et al., 2006). Additionally, dopamine is involved in the development of drug dependence and addiction (Volkow et al., 2009). To understand the mechanism by which dopamine mediates ethanol-induced behavioral disinhibition and sensitization, this study focused on the D1-family receptors dDA1 and DAMB, the insect homologs of mammalian D1 and D5 dopamine receptors, respectively. The major finding of this study is the essential role of DAMB receptor in alcohol-induced behavioral disinhibition. This may provide insight into new intervention strategies for alcohol abuse and addiction.
Mercado, Ivan, "The role of D1/dDA1 and D5/DAMB dopamine receptors in ethanol induced behavioral disinhibition" (2017). ETD Collection for University of Texas, El Paso. AAI10619648.