Temporally specific miRNA expression patterns in the dorsal and ventral striatum of addiction‐prone rats

Abstract

MicroRNAs (miRNAs) within the ventral and dorsal striatum have been shown to regulate addiction-relevant behaviours. However, it is unclear how cocaine experience alone can alter the expression of addiction-relevant miRNAs within striatal subregions. Further, it is not known whether differential expression of miRNAs in the striatum contributes to individual differences in addiction vulnerability. We first examined the effect of cocaine self-administration on the expression of miR-101b, miR-137, miR-212 and miR-132 in nucleus accumbens core and nucleus accumbens shell (NAcSh), as well as dorsomedial striatum and dorsolateral striatum (DLS). We then examined the expression of these same miRNAs in striatal subregions of animals identified as being 'addiction-prone', either immediately following self-administration training or following extinction and relapse testing. Cocaine self-administration was associated with changes in miRNA expression in a regionally discrete manner within the striatum, with the most marked changes occurring in the nucleus accumbens core. When we examined the miRNA profile of addiction-prone rats following self-administration, we observed increased levels of miR-212 in the dorsomedial striatum. After extinction and relapse testing, addiction-prone rats showed significant increases in the expression of miR-101b, miR-137, miR-212 and miR-132 in NAcSh, and miR-137 in the DLS. This study identifies temporally specific changes in miRNA expression consistent with the engagement of distinct striatal subregions across the course of the addiction cycle. Increased dysregulation of miRNA expression in NAcSh and DLS at late stages of the addiction cycle may underlie habitual drug seeking, and may therefore aid in the identification of targets designed to treat addiction.

An epigenetic, transgenerational model of increased mental health disorders in children, adolescents and young adults

“…These new set points and relative sensitization of specific brain circuits could contribute epigenetically to increased risk for MHD. In rodent models of stress, obesogenic diet, and substance misuse (methamphetamine, cocaine, and opioids), miRNA levels have been shown to be dynamically regulated in the ventral basal ganglia, and in the methamphetamine model, corresponded to specific shared miRNA levels in circulating serum exosomes [64][65][66][67][68].…”

Chronic calorie‐dense diet drives differences in motivated food seeking between obesity‐prone and resistant mice

“…Indeed, differences between structures in the reward system of obese and nonobese humans or rodents have been described, and it was suggested that obese individuals share behavioral and neurobiological similarities with those addicted to drugs . When examining rats after chronic exposure to cocaine, two populations can be identified—those that are prone to develop addiction and those that are resistant (some mouse models of addiction also reveal populations that differ in their motivation to obtain the reward, but these are not yet established for cocaine). In previous studies, others and we found that obesity‐prone rats show behavioral and neural properties similar to those of cocaine‐exposed rats .…”

MiR-9, miR-153 and miR-124 are down-regulated by acute exposure to cocaine in a dopaminergic cell model and may contribute to cocaine dependence

“…Moreover, overexpression of this gene in NAc attenuates cocaine-induced place preference in mice 51 . On the other hand, miR-137 and miR-101 are down-regulated in the NAc of cocaine self-administrated rats compared to controls 52 . This is the first time that miR-9-5p, miR-369-3p and miR-153-3p are found down-regulated after cocaine treatment.…”