Cocaine Modulates the Expression of Opioid Receptors and miR-let-7d in Zebrafish Embryos

Abstract

Prenatal exposure to cocaine, in mammals, has been shown to interfere with the expression of opioid receptors, which can have repercussions in its activity. Likewise, microRNAs, such as let-7, have been shown to regulate the expression of opioid receptors and hence their functions in mammals and in vitro experiments. In light of this, using the zebrafish embryos as a model our aim here was to evaluate the actions of cocaine in the expression of opioid receptors and let-7d miRNA during embryogenesis. In order to determine the effects produced by cocaine on the opioid receptors (zfmor, zfdor1 and zfdor2) and let-7d miRNA (dre-let-7d) and its precursors (dre-let-7d-1 and dre-let-7d-2), embryos were exposed to 1.5 µM cocaine hydrochloride (HCl). Our results revealed that cocaine upregulated dre-let-7d and its precursors, and also increased the expression of zfmor, zfdor1 and zfdor2 during early developmental stages and decreased them in late embryonic stages. The changes observed in the expression of opioid receptors might occur through dre-let-7d, since DNA sequences and the morpholinos of opioid receptors microinjections altered the expression of dre-let-7d and its precursors. Likewise, opioid receptors and dre-let-7d showed similar distributions in the central nervous system (CNS) and at the periphery, pointing to a possible interrelationship between them.In conclusion, the silencing and overexpression of opioid receptors altered the expression of dre-let-7d, which points to the notion that cocaine via dre-let-7 can modulate the expression of opioid receptors. Our study provides new insights into the actions of cocaine during zebrafish embryogenesis, indicating a role of miRNAs, let-7d, in development and its relationship with gene expression of opioid receptors, related to pain and addiction process.

MicroRNAs in Alcohol Abuse and Toxicity

“…However, ethanol is often coabused with other drugs, such as nicotine, cocaine, and marijuana. Yet another previously identified ethanol-sensitive miRNA, let-7, has been also found to be altered following cocaine exposure in a developmental zebrafish model (Lopez-Bellido, Barreto-Valer, Sanchez-Simon, & Rodriguez, 2012). Are there common miRNA targets of drug abuse?…”

“…Some miR-NAs, such as miR-21, the miR-1/miR-206 family, and the let-7 family, have been identified as a component of the miRNA response to ethanol exposure (Lewohl et al, 2011;Sathyan et al, 2007;Tapocik et al, 2013) and to other drugs of abuse (Lopez-Bellido et al, 2012) and are also regulated in other conditions of neural trauma, including spinal cord trauma (Strickland et al, 2011) and stroke (Selvamani, Sathyan, Miranda, & Sohrabji, 2012). Moreover, miRNAs play an important role in ethanol neurotoxicology and neuroteratology.…”

Combined Biomarkers Composed of Environment and Genetic Factors in Stroke

“…Cocaine up-regulated let-7d in zebrafish embryos (32). The repressing of mir-21 could attenuate bleomycin-induced pulmonary fibrosis (33). mir-122 was shown to be up-regulated during apoptosis induced by bortezomib and sensitized hepatocellular carcinoma cells to sorafenib (27,34).…”

MicroRNAs as regulators of drug abuse and immunity

“…Chronic cocaine exposure also increases miR-181a expression [18–20]. Aberrant expression of miR-181a, which binds to the 3’-UTR of the GluA2 subunit of the AMPA receptor (GRIA2), influences the function of the GABA system [21].…”