Opioid Dependence Found to Permanently Change Brains of Rats
upstart writes in with an IRC submission for Bytram:
Opioid dependence found to permanently change brains of rats:
Approximately one-quarter of patients who are prescribed opioids for chronic pain misuse them, with five to 10 percent developing an opioid use disorder or addiction. In a new study, published Jan. 14, 2020 in PNAS, researchers at University of California San Diego School of Medicine found that opioid dependence produced permanent changes in the brains of rats.
More specifically, researchers reported that dependence on oxycodone, a potent opioid painkiller, led to permanent neuro-adaptations of the central nucleus of the amygdala (CeA) at the level of the nociceptin system, a brainwide network that modulates transmission of pain. Downregulation or suppression of the nociceptin system in the CeA led to an increase in activation of GABA receptors in rats highly addicted to opioids. The discovery is consistent with previous findings reporting CeA neuroa-daptations after cocaine and alcohol dependence.
When researchers restored nociceptin levels in the CeA, it resulted in normalization of GABAergic transmission and a reduction of the rats' opioid consumption.
"This suggests the nociceptin system may be a promising target for the treatment of opioid use disorder," said senior author Giordano de Guglielmo, PharmD, PhD, assistant professor in the Department of Psychiatry at UC San Diego School of Medicine.
"To reveal the role of nociceptin in the central nucleus of the amygdala, we used a multidisciplinary approach with behavioral models, molecular biology and electrophysiology," said first author Marsida Kallupi, PharmD, PhD, assistant professor in the Department of Psychiatry. "That allowed us to conclude that downregulation of this peptide may be partially responsible for excessive opioid addiction-like behaviors."
Marsida Kallupi, Lieselot L. G. Carrette, Jenni Kononoff, Leah C. Solberg Woods, Abraham A. Palmer, Paul Schweitzer, Olivier George, Giordano de Guglielmo. Nociceptin attenuates the escalation of oxycodone self-administration by normalizing CeA-GABA transmission in highly addicted rats. Proceedings of the National Academy of Sciences, 2020; 201915143 DOI: 10.1073/pnas.1915143117
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