NIH Research Festival
Over the last two decades, opioid overdose has become the third leading cause of accidental deaths in the United States. Recent evidence suggests that glial activation and the related neuroimmune signals may be involved in the dependence-inducing properties of opioids. Therefore, the main purpose of this study is to investigate the role of neuroimmune systems in opioid withdrawal-related behavior in rats. We first measured hyperalgesia and the aversive effects of heroin withdrawal in adult male and femaleWistar rats. Hyperalgesia was assessed using von Frey and Hargreaves tests, for mechanical and thermal sensitivity, respectively, after two weeks of repeated heroin administration. We also investigated the heroin withdrawal-induced conditioned place aversion (CPA) and naloxone-precipitated somatic withdrawal. Then, we quantified 17 cytokines and chemokines in whole brains of both saline- and heroin-treated rats by a FirePlex immunoassay. The data showed that two chemokines (CCL2 and CXCL1) and a cytokine (IL-10) were significantly upregulated in male rats that received heroin but not in females. Based on these results, we investigated whether an acute injection of a CCL2 antagonist could reverse the heroin-induced hyperalgesia, CPA and somatic withdrawal symptoms in heroin-dependent male and female Wistar rats. Results showed that the antagonist significantly reversed mechanical and thermal hyperalgesia, and attenuated CPA and somatic withdrawal symptoms in males and females. In summary, our findings suggest a sex-dependent proinflammatory effect of heroin withdrawal in the rat brain. Our data also shows that CCL2 may contribute to motivational and somatic signs of opioid withdrawal in adult Wistar rats.
Scientific Focus Area: Neuroscience
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