Abstract Details

Title Opioid Withdrawal Shifts Amygdalar Transcriptome and is Correlated with Gut Dysbiosis

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P1 - Poster Session 1 (5:30 PM-6:30 PM)

Poster/Presentation
Number 9-031

Objective We investigated glial-neuronal signaling networks via single-cell transcriptomic measures in the central nucleus of the amygdala (CeA) that occur in chronic morphine exposure and withdrawal. We hypothesize local glial-neuronal signaling in the CeA underlie the negative emotional state experienced in opioid withdrawal which contributes to habitual use via negative reinforcement.

Background Opioid withdrawal involves a spectrum of physiological activity that largely manifests in dysphoria, nausea, anxiety and fear. The negative-reinforcement model of addiction postulates that avoidance of these negative physical and emotional symptoms drives drug-seeking. The amygdala plays a central role in this process because it is a limbic structure responsible for fear and anxiety that also processes autonomic inputs, generates autonomic outputs, and has consistently demonstrated involvement in addiction and motivated behaviors.

Design/Methods We use a single-cell in vivo approach that combines the anatomic specificity of laser capture microdissection (LCM) with the reproducibility of RT-qPCR. We lifted single neurons, microglia and astrocytes from the CeA of rats from chronic moderate morphine exposure and naltrexone-precipitated withdrawal and measured a subset of their transcriptome.

Results

We observe that six days of chronic moderate morphine exposure does not have a large impact on the transciptional state of single neurons, microglia, and astrocytes in the CeA but that withdrawal from morphine does. Strikingly, astrocytes demonstrated the most profound shift in transcription. In addition, significant upregulation of the proinflammatory cytokine Tnf-α was observed in all three cell types assayed suggesting local paracrine signaling in the CeA during opioid withdrawal is shifted towards a neuroinflammatory state.

Conclusions We speculate the negative emotions experienced in opioid withdrawal are driven, in part, by neuroinflammatory glial-neuronal signaling in the CeA. Our findings in context with the work of others are consistent with this conjecutre though further investigation is required to confirm these observations.

Authors/Disclosures
Sean S. O'Sullivan, MD (Precision Neurology Unlimited Company) PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file

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