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MicroRNA-31-3p/RhoA signaling in the dorsal hippocampus modulates methamphetamine-induced conditioned place preference in mice.
- Source :
-
Psychopharmacology [Psychopharmacology (Berl)] 2021 Nov; Vol. 238 (11), pp. 3207-3219. Date of Electronic Publication: 2021 Jul 27. - Publication Year :
- 2021
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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.<br />Objective: To explore the molecular biology and epigenetic mechanisms of the miR-31-3p/RhoA pathway in METH addiction.<br />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.<br />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.<br />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.<br /> (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Details
- Language :
- English
- ISSN :
- 1432-2072
- Volume :
- 238
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Psychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 34313802
- Full Text :
- https://doi.org/10.1007/s00213-021-05936-2