Alterations of prefrontal cortical microRNAs in methamphetamine self-administering rats: From controlled drug intake to escalated drug intake

• 28 differential miRNAs were screened in controlled or escalated methamphetamine use.
• miR-186 increased and miR-195, -329 decreased in PFC of controlled drug use rats.
• miR-127, -186, -222, -24 increased and miR-329 decreased in escalated drug use rats.
• Predicted targets functionally clustered in neural apoptosis and synaptic plasticity.

Drug addiction is a process that transits from recreative and regular drug use into compulsive drug use. The two patterns of drug use, controlled drug intake and escalated drug intake, represent different stages in the development of drug addiction; and escalation of drug use is a hallmark of addiction. Accumulating studies indicate that microRNAs (miRNAs) play key regulatory roles in drug addiction. However, the molecular adaptations in escalation of drug use, as well as the difference in the adaptations between escalated and controlled drug use, remain unclear. In the present study, 28 altered miRNAs in the prefrontal cortex (PFC) were found in the groups of controlled methamphetamine self-administration (1 h/session) and escalated self-administration (6 h/session), and some of them were validated. Compared with saline control group, miR-186 was verified to be up-regulated while miR-195 and miR-329 were down-regulated in the rats with controlled methamphetamine use. In the rats with escalated drug use, miR-127, miR-186, miR-222 and miR-24 were verified to be up-regulated while miR-329 was down-regulated compared with controls. Furthermore, bioinformatic analysis indicated that the predicted targets of these verified miRNAs involved in the processes of neuronal apoptosis and synaptic plasticity. However, the putative regulated molecules may be different between controlled and escalated drug use groups. Taken together, we detected the altered miRNAs in rat PFC under the conditions of controlled methamphetamine use and escalated use respectively, which may extend our understanding of the molecular adaptations underlying the transition from controlled drug use to addiction.