Molecular, Cellular, and Structural Mechanisms of Cocaine Addiction: A Key Role for MicroRNAs

Abstract

The rewarding properties of cocaine play a key role in establishing and maintaining the drug-taking habit. However, as exposure to cocaine increases, drug use can transition from controlled to compulsive. Importantly, very little is known about the neurobiological mechanisms that control this switch in drug use that defines addiction. MicroRNAs (miRNAs) are small non-protein coding RNA transcripts that can regulate the expression of messenger RNAs that code for proteins. Because of their highly pleiotropic nature, each miRNA has the potential to regulate hundreds or even thousands of protein-coding RNA transcripts. This property of miRNAs has generated considerable interest in their potential involvement in complex psychiatric disorders such as addiction, as each miRNA could potentially influence the many different molecular and cellular adaptations that arise in response to drug use that are hypothesized to drive the emergence of addiction. Here, we review recent evidence supporting a key role for miRNAs in the ventral striatum in regulating the rewarding and reinforcing properties of cocaine in animals with limited exposure to the drug. Moreover, we discuss evidence suggesting that miRNAs in the dorsal striatum control the escalation of drug intake in rats with extended cocaine access. These findings highlight the central role for miRNAs in drug-induced neuroplasticity in brain reward systems that drive the emergence of compulsive-like drug use in animals, and suggest that a better understanding of how miRNAs control drug intake will provide new insights into the neurobiology of drug addiction.

Functions of microRNA in response to cocaine stimulation

“…Among them, the expression level of miR-212 was found to be highly expressed after cocaine treatment, proving its key role in the regulatory mechanism for cocaine addiction. These results were also in accordance with previous studies (Robison and Nestler, 2011;Jonkman and Kenny, 2013).…”

Enhancing glutamatergic transmission during adolescence reverses early-life stress-induced deficits in the rewarding effects of cocaine in rats

“…Long-term drug use induces alterations to neurochemical and molecular signalling cascades in reward pathways which precipitate further seeking and intake of the drug (Jonkman and Kenny, 2013;Koob, 2009;Lupien, 2014;Van Dam et al, 2014). This pattern of drug intake is pervasive, disabling, and greatly impairs the quality of life of an individual.…”

Chronic Administration of Δ 9 -Tetrahydrocannabinol Induces Intestinal Anti-Inflammatory MicroRNA Expression during Acute Simian Immunodeficiency Virus Infection of Rhesus Macaques

“…Several recent reports have linked altered microRNA (miRNA) expression, a newly identified class of noncoding RNAs that function to regulate gene expression to alcohol, morphine, and cocaine addiction (25)(26)(27)(28)(29).…”