From Flies to Humans: Circadian Genes in the Neurogenetics of Addiction

Drug addiction is a persistent brain disease with severe and sometimes fatal consequences. Addictive drugs induce long-lasting neuroadaptations in the functioning of the nervous system and currently there is no efficient pharmacological treatment that can successfully prevent or reverse these changes. As a consequence, addicted individuals often suffer from recurrent relapses, sometimes triggered by environments, situations or stressors that have previously been associated with drug taking. Behavioral neuroscience uses animal models to understand the neurobiological mechanisms which cause and correlate with the development of addiction, and recently the emphasis is on animals that are genetically tractable, such as mice (Mus musculus) and fruit flies, (Drosophila melanogaster). In spite of many obvious differences between humans and Drosophila, similarities at the genetic level and in the basic neuronal physiology, make Drosophila an excellent model organism for the study of many complex human behaviors, including addiction. Discovery that circadian genes influence the development of behavioral sensitization to cocaine in Drosophila led to numerous studies about the role of circadian genes in the regulation of drug-induced behaviors in laboratory mammals and humans. Results show that circadian genes are involved in regulating the behavioral and molecular response to different classes of drugs of abuse. Furthermore, studies in humans show the interconnectivity between the regulation of circadian behavior, mental diseases and addiction, and suggest that behavioral interventions aimed at improving the quality of the circadian behavior will be important in prevention and treatment of addictive behaviors.