Abstract
Drug-seeking in opioid dependence is due in part to the severe negative emotion associated with the withdrawal syndrome. It is well-established that negative emotional states emerge from activity in the amygdala. More recently, gut microflora have been shown to contribute substantially to such emotions. We measured gene expression in single glia and neurons gathered from the amygdala using laser capture microdissection and simultaneously measured gut microflora in morphine-dependent and withdrawn rats to investigate drivers of negative emotion in opioid withdrawal. We found that neuroinflammatory genes, notably Tnf, were upregulated in the withdrawal condition and that astrocytes, in particular, were highly active. We also observe a decreased Firmicutes to Bacteroides ratio in opioid withdrawal indicating gut dysbiosis. We speculate that these inflammatory and gut microflora changes contribute to the negative emotion experienced in opioid withdrawal that motivates dependence.
Highlights
Opioid dependence has grown at an alarming rate over the past decade
The central nucleus of the amygdala (CeA) is a limbic hub involved in autonomic regulation, emotion, and motivated behavior, and has been strongly implicated in opioid dependence (Koob, 2009a; Upadhyay et al, 2010)
We found that 6 days of chronic moderate morphine exposure does not substantially influence the transcriptional state of single neurons, microglia, and astrocytes in the CeA but that morphine withdrawal does
Summary
Opioid dependence has grown at an alarming rate over the past decade. Rehabilitation services are overwhelmed (Sigmon, 2014) and maintenance therapies have proven their value and limitations (Stotts et al, 2009). These circumstances motivate investigation into non-canonical mechanisms of addiction pathophysiology to identify novel treatment targets. Inflammation has been shown to play a role in drug dependence (Coller and Hutchinson, 2012). Opioids have been shown to increase central cytokine and chemokine production, and the mechanisms explaining this phenomenon are coming to light (Peterson et al, 1998; Wang et al, 2012; Jacobsen et al, 2016).
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