UC San Diego

The Locus Coeruleus (LC) is the major source of noradrenaline in the brain and sends distinct projections to supraspinal brain structures and the spinal cord. While ascending projections from the dorsal LC are implicated in anxiogenic and aversive behavior, descending projections from the ventral LC to the dorsal horn of the spinal cord mediate noradrenaline-induced analgesia. In the LC, administration of opioid analgesics increases potassium channel conductance, leading to membrane hyperpolarization and decreased neuronal firing. Yet, why opioid analgesics paradoxically inhibit a major center for noradrenaline-mediated analgesia is unclear. The answer to this may lie in differential transcription of the mu opioid receptor (MOR) along the dorsal-ventral axis of the LC. We hypothesized that the dorsal portion of the LC, responsible for anxiety-generating behavior, may display higher quantities of MOR RNA transcripts compared to the analgesia-mediating ventral portion of the LC. To elucidate if MOR transcription in the LC follows a dorsal-ventral gradient, we performed RNA in situ hybridization on the LC. However, quantification of MOR transcripts in the LC showed no obvious dorsal-ventral gradient of MOR. This suggests that the answer to the paradoxical effect of opioids in the LC does not lie in inhomogeneous MOR transcription along its dorsal-ventral axis.