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MicroRNA-31-3p/RhoA signaling in the dorsal hippocampus modulates methamphetamine-induced conditioned place preference in mice.
- Source :
-
Psychopharmacology . Nov2021, Vol. 238 Issue 11, p3207-3219. 13p. 2 Charts, 5 Graphs. - Publication Year :
- 2021
-
Abstract
- Rationale: MicroRNAs (miRNAs) regulate neuroplasticity-related proteins and are implicated in methamphetamine (METH) addiction. RhoA is a small Rho GTPase that regulates synaptic plasticity and addictive behaviors. Nevertheless, the functional relationship between RhoA and upstream miRNAs of METH addiction remains unclear. Objective: To explore the molecular biology and epigenetic mechanisms of the miR-31-3p/RhoA pathway in METH addiction. Methods: RhoA protein and its potential upstream regulator, miR-31-3p, were detected. A dual luciferase reporter was employed to determine whether RhoA constituted a specific target of miR-31-3p. Following adeno-associated virus (AAV)-mediated knockdown or overexpression of miR-31-3p or RhoA in the dorsal hippocampus (dHIP), mice were subjected to conditioned place preference (CPP) to investigate the effects of miR-31-3p and RhoA on METH-induced addictive behaviors. Results: RhoA protein was significantly decreased in the dHIP of CPP mice with a concomitant increase in miR-31-3p. RhoA was identified as a direct target of miR-31-3p. Knockdown of miR-31-3p in the dHIP was associated with increased RhoA protein and attenuation of METH-induced CPP. Conversely, overexpression of miR-31-3p was associated with decreased RhoA protein and enhancement of METH effects. Similarly, knockdown of RhoA in the dHIP enhanced METH-induced CPP, whereas RhoA overexpression attenuated the effects of METH. Parallel experiments using sucrose preference revealed that the effects of miR-31-3p/RhoA pathway modulation were specific to METH. Conclusions: Our findings indicate that the miR-31-3p/RhoA pathway in the dHIP modulates METH-induced CPP in mice. Our results highlight the potential role of epigenetics represented by non-coding RNAs in the treatment of METH addiction. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00333158
- Volume :
- 238
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Psychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 153682964
- Full Text :
- https://doi.org/10.1007/s00213-021-05936-2