MiR-33-5p Regulates CREB to Induce Morphine State-dependentMemory in Rats: Interaction with the μ Opioid Receptor

Document Type : Original Article

Authors
Sadegh Moradi Vastegani 1
Behrang Alani 2
Khatereh Kharazmi 1
Abolfazl Ardjmand 3 , 4
1 Institute for Basic Sciences, Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran.
2 Department of Applied Cell Sciences, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
3 Institute for Basic Sciences, Physiology Research Center, Kashan University of Medical Sciences, Kashan, Iran
4 Department of Physiology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
10.22088/IJMCM.BUMS.11.2.150
Abstract
The aim of the present study was to examine the hypothesis that miR-33-5p attenuates
morphine state-dependent (StD) memory via the μ opioid receptor by regulating cyclic
AMP response element-binding protein (CREB). The effects of post-training morphine
and morphine StD memory and their interaction with pre-test naloxone were evaluated
using a single-trial inhibitory avoidance paradigm. Then, the hippocampal miR-33-5p
gene and pCREB/CREB protein expression profiles were evaluated using quantitative
real-time PCR and western blotting, respectively. We found that while post-training
morphine and morphine StD memory respectively up- and down-regulate the miR-33-5p
expression profile in the hippocampus, the reverse results are true for the expression of
pCREB/CREB. Pre-test naloxone antagonized the response. Overall, our findings suggest
that the expression levels of miR-33-5p in the hippocampus set the basis for morphine StD
memory with low miR-33-5p enabling state dependency. The mechanism is mediated via
miR33-5p and CREB signaling with the interaction of the μ opioid receptor. This finding
may be used as a potential strategy for ameliorating morphine-induced memory-related
disorders.
Keywords
miR-33-5p
CREB
state-dependent memory
opioids
Rats