MicroRNA‐132 is involved in morphine dependence via modifying the structural plasticity of the dentate gyrus neurons in rats

Abstract

Repeated morphine exposure has been shown to induce neuronal plasticity in reward‐related areas of the brain. miR‐132, a CREB‐induced and activation‐dependent microRNA, has been suggested to be involved in the neuronal plasticity by increasing neuronal dendritic branches and spinogenesis. However, it is still unclear whether miR‐132 is related to morphine dependence. Here, we investigate whether miR‐132 is involved in morphine dependence and whether it is related to the structural plasticity of the dentate gyrus (DG) neurons. Sprague–Dawley rats are treated with increasing doses of morphine injection for six consecutive days to develop morphine dependence. Our results show that dendritic branching and spinogenesis of the DG neurons of morphine dependent rats are increased. Morphine treatment (24 h) promotes the differentiation of N2a cells stably expressing μ‐opioid receptor by up‐regulating miR‐132 expression. Moreover, inhibiting miR‐132 3p (but not 5p) of the DG neurons can reverse the structural plasticity and disrupt the formation of morphine dependence in rats. These findings indicate that miR‐132 in the DG neurons is involved in morphine dependence via modifying the neuronal plasticity.

Role of microRNA-132 in Opioid Addiction through Modification of Neural Stem Cell Differentiation

“…Interestingly, Jia and colleagues recently carried out another study, in which it was noted that in vitro morphine exposure (for 24 h) promotes the differentiation of N2a cells that express the µ-opioid receptor via the upregulation of miR-132 expression. They also observed that in vivo morphine dependence was clearly associated with increased miR-132 expression and neuronal structural plasticity in the DG neurons of rats [33]. These findings again demonstrated a specific link between miR-132 expression and changes in neuronal structure and function upon opioid exposure.…”

Dopamine D4 Receptor Is a Regulator of Morphine-Induced Plasticity in the Rat Dorsal Striatum

“…This observation is consistent with previous reports describing a similar pattern of long-term morphine-induced structural plasticity in several regions belonging to the reward circuit [ 2 , 5 , 12 , 45 ]. However, more recent studies have highlighted some contradictory data depicting an opposite effect, especially in the NAc, the orbital prefrontal cortex and the dentate gyrus of the hippocampus [ 13 , 14 , 15 , 46 ]. These differences could be attributed to several factors, such as the paradigm of drug administration, the animal sacrifice time point, the brain region analyzed, or even the cell type studied.…”

Molecular and Epigenetic Aspects of Opioid Receptors in Drug Addiction and Pain Management in Sport

“…A combined in vivo/in vitro study by Jan and coworkers [142] revealed that morphine dependence increased the expression of miRNA132-a CREB-induced and activationdependent microRNA-in the dentate gyrus of rats promoting dendritic branching and spinogenesis; in turn, the inhibition of miRNA132-3p but not miRNA132-5p relieved mor-phine withdrawal symptoms. Consistently, in an in vitro model of µ-N2a cells that stably express MOR receptor, 24 h morphine treatment up-regulated miRNA132, promoting their differentiation [142]. Thus, miRNA132 in the hippocampus participates in morphine dependence modifying neuronal plasticity.…”

“…Morphine withdrawal symptoms miRNA132-3p - [142] Reconsolidation of cocaine-associated memory circTmeff-1 miRNA206 BDNF [155] BDNF: Brain-derived neurotrophic factor; Btg2: BTG anti-proliferation factor 2; Cd69: CD69 molecule; Cldn11: claudin 11; DRD2: dopamine D2 receptor; REST: RE1-silencing transcription factor; Tmeff-1: tomoregulin-1; -: not tested.…”