In vivo effects of morphine on neuronal fate and opioid receptor expression in zebrafish embryos

Abstract

Morphine remains one of the most potent analgesic compounds used to control chronic pain despite its known adverse effects. It binds to the opioid receptors mu, delta and kappa, which are involved in aspects of neuronal fate such as cell proliferation, neuroprotection and neuronal differentiation. However, the effect of morphine on these processes is controversial and in vitro studies, as well as in vivo studies on adults and neonates in mammalian models, have not been able to clarify the diverse roles of morphine in the central nervous system. We have used zebrafish embryos to determine in vivo how morphine affects neuronal fate and opioid receptor gene expression and to elucidate if there is a link between these processes. Our results show that at 24 and 48 h post fertilization (hpf) morphine enhances cell proliferation, although it has opposing effects as an inducer of neuronal differentiation at these two stages, increasing the number of certain neuronal populations at 24 hpf and decreasing it at 48 hpf. The present study also demonstrates that in 24-hpf embryos morphine acts as a neuroprotector against glutamate damage in motor neurons and Pax-6-positive neurons. Furthermore, the gene expression of the opioid receptors is altered by embryonic exposition to morphine. In conclusion, our study sheds new light on the in vivo roles of morphine, and it indicates for the first time that its implication in cell proliferation and neuroprotection might be related to changes in the gene expression of opioid receptors.

Effects of chronic tramadol exposure on the zebrafish brain: A proteomic study

“…The zebrafish represents a straightforward model to discover and validate new pharmacological targets, as well as to find new drugs, to perform toxicological tests, and to analyze the biological effects of several drugs of abuse, such as cocaine [26], ethanol [27,28], and morphine [29], and the results are similar to those found in mice. Therefore, in this study, combining multiple methods, including behavioral observation, drug and metabolite detection, Western blot Real-Time reverse transcription PCR (RT-PCR), enzyme activity assay, and ultrastructural observation with proteomic technologies was used to screen and identify tramadolassociated key proteins in the zebrafish brain.…”

Morphine pre- and post-conditioning exacerbates apoptosis in rat hippocampus cells in a model of homocysteine-induced oxidative stress

“…In zebra fish embryos, morphine at certain concentrations, enhances neuron proliferation and the number of certain neuronal populations and also protects against glutamate damage in motor neurons and Pax-6-positive neurons in vivo (3). In addition, morphine is protective against microglia-mediated lipopolysaccharide-or 1-methyl-4-phenylpyridinium-induced dopaminergic neurotoxicity in rat primary mesencephalic neuron/glia cultures (4).…”

Morphine Protects against Intracellular Amyloid Toxicity by Inducing Estradiol Release and Upregulation of Hsp70

“…In rat neonatal hypoxia-ischemia model, morphine application immediately after hypoxia decreases infarct volume in the brain (Zhou et al, 1998). In zebrafish embryos, morphine, at certain concentrations, enhances neuron proliferation, increases the number of certain neuronal populations, and protects against glutamate damage in motor neurons and Pax-6-positive neurons in vivo (Sanchez-Simon et al, 2010). Morphine is found to be protective against microglia-mediated lipopolysccharide-or 1-methyl-4-phenylpyridinium-induced dopaminergic neurotoxicity in rat primary mesencephalic neuron/glia cultures (Qian et al, 2007).…”