De moscas a humanos: Genes circadianos en la neurogenética de la adicción

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.Ovisnost je o drogama kronična bolest s teškim, nerijetko fatalnim posljedicama. Opojne droge izazivaju dugotrajne neuroadaptivne promjene u funkcioniranju živčanog sustava, a ne postoji učinkovit lijek koji bi ih suzbio ili ispravio. Ovisnici stoga pate od opetovanih recidiva, ponekad izazvanih okolinom, situacijom ili stresom koji je i bio povezan s uzimanjem droge.Bihevioralna neuroznanost koristi modelne organizme za razumijevanje neurobioloških mehanizama koji uvjetuju ili koreliraju s razvojem ovisnosti, a odnedavno naglasak je na životinjama koje su genetski pogodne, kao miš (Mus musculus) ili vinska mušica (Drosophila melanogaster). Unatoč mnogim očitim razlikama između ljudi i Drosophile sličnosti na genetskoj razini i u području bazične neuronske fiziologije čine Drosophilu izvrsnim modelnim organizmom za izučavanje mnogih složenih ljudskih ponašanja, uključujući ovisnost. Otkriće da cirkadijalni geni kontroliraju razvoj bihevioralne senzitizacije na kokain kod Drosophile potaklo je niz istraživanja o ulozi koju cirkadijalni geni imaju u ponašanjima induciranim kokainom kod laboratorijskih životinja i ljudi. Rezultati pokazuju da cirkadijalni geni reguliraju ponašanja i molekularne odgovore na razne vrste opojnih droga. Štoviše, istraživanja na ljudima upućuju na međupovezanost između cirkadijalnog ponašanja, mentalnih oboljenja i ovisnosti, te sugeriraju da bihevioralni zahvati usmjereni na poboljšanje cirkadijalnog ponašanja mogu biti važni u prevenciji i liječenju ovisničkog ponašanja.La drogadicción es una de las enfermedades crónicas con consecuencias graves, a veces fatales. Las drogas adictivas causan cambios neuroadaptivos a largo plazo en el funcionamiento del sistema nervioso y de momento no existe un medicamento eficiente que lo reprimiría o corregiría. Por eso los drogadictos sufren repetidas recaídas, a veces causadas por el entorno, situación o estrés previamente relacionado con el consumo de drogas.Neurociencia conductual usa organismos modelos para comprender mecanismos neurobiológicos que condicionan o se correlacionan con el desarrollo de la adicción, y recientemente el enfoque está en los animales genéticamente convenientes, como ratón (Musmusculus) o mosca del vinagre (Drosophila melanogaster). A pesar de las numerosas diferencias obvias entre los humanos y las moscas del vinagre, la semejanza al nivel genético y aquel de fisiología neuronal básica convierten dicha mosca del vinagre en un excelente organismo modelo para estudiar muchas conductas humanas complejas, incluida la adicción. Al descubrir que los genes circadianos controlan el desarrollo de la sensibilización de comportamiento de la mosca del vinagre en cuanto a la cocaína, se provocó toda una serie de investigaciones sobre el papel que tienen los genes circadianos para los comportamientos inducidos por la cocaína tanto en los animales de laboratorio, como en los humanos. Los resultados indican que los genes circadianos regulan comportamientos y respuestas moleculares a diferentes tipos de drogas adictivas. Es más, las investigaciones en los humanos muestran la interconexión entre el comportamiento circadiano, enfermedades mentales y adicción, y proponen que las intervenciones en el comportamiento enfocadas en la mejora del comportamiento circadiano pueden ser importantes en la prevención y tratamiento de conductas adictivas