The effects of µ-opioid receptor activation on GABAergic synaptic transmission within the orbital frontal cortex
Date
2019-01-09
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Abstract
The orbital frontal cortex (OFC) plays a critical role in evaluating outcomes in a changing environment. Several studies have demonstrated that administering opioids can alter reward valuation and action selection. More specifically, µ-opioid activation within the OFC has been shown to enhance both consumption of food rewards and the hedonic reaction to them. Mechanistically, there is ample evidence confirming that µ-opioid agonists act pre-synaptically to disinhibit the output of other cortical regions; however, the precise cellular mechanism of µ-opioid signalling across the OFC remains unknown. Thus, we investigated the cellular actions of µ-opioids within the medial and lateral OFC. Using in-vitro patch clamp electrophysiology in brain slices containing the OFC, I found a dose-dependant effect of µ-opioid receptor (MOR) activation on GABAergic synaptic transmission within the medial, but not lateral, OFC. Furthermore, this effect occurred via decreased pre-synaptic release probability of GABA onto pyramidal neurons, consistent with actions of µ-opioids in other cortical regions. Preliminary data also suggest µ-opioid agonists are acting on parvalbumin-positive subpopulations of interneurons. The findings of this study further elucidate the effects of MOR activity on synaptic transmission within the OFC, which remains largely understudied. Importantly, understanding the interaction between the OFC and the opioid system may reveal new mechanisms of action in disorders of aberrantly motivated behaviours.
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Keywords
Orbital frontal cortex, opioid, DAMGO, µ-opioid receptor, inhibitory synaptic transmission
Citation
Ambrose, B. P. (2019). The effects of µ-opioid receptor activation on GABAergic synaptic transmission within the orbital frontal cortex (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.