Kappa opioid receptor modulation on GABAergic inputs onto ventral periaqueductal gray dopamine neurons

The kappa opioid receptor (KOR) system has been implicated in regulation of many behaviors including pain. While there are numerous studies suggesting KOR-regulation of pain being mediated spinally, there have been reports of pain-like behaviors regulated by central KOR signaling. In particular, oxytocin-induced analgesia appears to be mediated by KOR receptors within the ventrolateral periaqueductal gray (vlPAG). The vlPAG is a brain region that has long been known to be involved in the regulation of pain. We recently found that dopamine (DA) neurons within the vlPAG represent a specific population of neurons that can regulate pain-like behaviors. In this study, we sought to determine the impact of KOR signaling on GABAergic inputs to the vlPAG DA neurons, and determine the mechanism of inhibition. We found that activation of KOR significantly reduced GABAergic transmission onto vlPAG DA neurons. In addition, our data suggest this effect is mediated pre-synaptically via the G-protein βγ subunit. These data suggest the possibility that KOR-activation disinhibits vlPAG dopamine neurons, which could lead to altered regulation of pain-related behaviors.