New insights into the roles of microRNAs in drug addiction and neuroplasticity

Abstract

Drug addiction is a major public health issue. It is typically a multigenetic brain disorder, implying combined changes of expression of several hundred genes. Psychostimulants (such as cocaine, heroin and amphetamines) induce strong and persistent neuroadaptive changes through a surfeit of gene regulatory mechanisms leading to addiction. Activity-dependent synaptic plasticity of the mesolimbic dopaminergic system, known as the 'reward pathway', plays a crucial role in the development of drug dependence. miRNAs are small non-coding RNAs, particularly abundant in the nervous system, that play key roles as regulatory molecules in processes such as neurogenesis, synapse development and plasticity in the brain. They also act as key spatiotemporal regulators during dendritic morphogenesis, controlling the expression of hundreds of genes involved in neuroplasticity and in the function of synapses. Recent studies have identified changes of several specific miRNA expression profiles and polymorphisms affecting the interactions between miRNAs and their targets in various brain disorders, including addiction: miR-16 causes adaptive changes in production of the serotonin transporter; miR-133b is specifically expressed in midbrain dopaminergic neurons, and regulates the production of tyrosine hydroxylase and the dopamine transporter; miR-212 affects production of striatal brain-derived neurotrophic factor and synaptic plasticity upon cocaine. Clearly, specific miRNAs have emerged as key regulators leading to addiction, and could serve as valuable targets for more efficient therapies. In this review, the aim is to provide an overview of the emerging role of miRNAs in addiction.