University of Puerto Rico, Río Piedras Campus
Molecular Cell Biology
Mentor: Dr. Alfredo Ghezzi; University of Puerto Rico, Río Piedras Campus
Project: Defining the role of NMDAR1 in Alcohol Use Disorder
Description of Project: Alcohol addiction or Alcohol Use Disorder (AUD) is defined as an increase in the desire to consume alcohol accompanied by an impaired ability to stop or control use. Sustained exposure to drugs leads to adaptations in the brain caused by changes in gene expression. This genetic plasticity is involved in the persistence of symptoms of alcohol addiction even after extended periods of abstinence and give rise to behavioral phenotypes such as tolerance and dependence. The N-methyl-D-aspartate ionotropic receptor (NMDAR) interacts with the major excitatory amino acid called glutamate and possess many functional processes such as synaptic plasticity, learning and memory. Acute alcohol exposure inhibits the excitatory action of glutamate at NMDA receptors and blocks Brain-derived neurotrophic factor (BDNF) at post-synaptic levels, acting ethanol as an antagonist. We use a combination of behavioral and genetic analyses in a Drosophila model system to characterize the effect of sleep response in NMDAR gene repression via RNAinterference (RNAi) on alcohol exposed fly behavior. It is known that an exposure to alcohol increased fly sleep and decreases locomotion in female flies. Additionally, mutant flies expressing an RNAi for the NR1 subunit of the NMDA receptor coded by Nmdar1 revealed an increase in locomotion in the fly female mutants when compared to the controls. The effect of ethanol in these receptors will allow us to gain a better understanding of how BDNF at the transcriptional level is being affected. Further, this inhibition of NMDA-mediated modulation of locomotor activity might explain therapeutic potentials for treatment of Alcohol Abuse Disorder.