Tolerance in Thalamic Paraventricular Nucleus Neurons Following Chronic Treatment of Animals with Morphine.

Neurons in the paraventricular nucleus of the thalamus (PVT) integrate visceral and limbic inputs and project to multiple brain regions to bias behavior toward aversive or defensive states. This study examines MOR signaling in anterior PVT neurons in brain slices from untreated and morphine-treated animals. Imaging in a MOR-Cre reporter rat revealed extensive expression in aPVT cells, and the application of [Met](5-) enkephalin (ME) induced outward currents which were abolished by the MOR-selective antagonist CTAP. A saturating concentration of ME resulted in desensitization that was blocked by compound 101, indicating a phosphorylation-dependent process. The opioid sensitivity of amygdala-, nucleus accumbens-, and prefrontal cortex-projecting neurons was then examined. Neurons that projected to the amygdala were more sensitive to ME than cortical- and accumbal-projecting cells. Following chronic treatment, tolerance to morphine was found in neurons projecting to the amygdala and nucleus accumbens with a trend toward tolerance observed in neurons projecting to the prefrontal cortex. The results reveal that adaptations to chronic opioid exposure are in the aPVT circuits contribute to affective pain processing and may provide specific insights into the etiology of withdrawal following the cessation of opioid use.