Chronic morphine treatment induces functional delta-opioid receptors in amygdala neurons that project to periaqueductal grey.

Chronic morphine treatment and persistent pain stimuli trigger translocation of delta-opioid receptors (DORs) from cytosolic pools to the surface membrane. Previously, we reported that chronic treatment with morphine induces functional DORs on GABAergic nerve terminals impinging on some neurons in the midbrain periaqueductal grey. In the present investigation, we used chronic administration of morphine in adult rats to study delta and mu-opioid receptors in the central nucleus of amygdala (CeA), a brain region with a substantial (presumed) GABAergic projection to the periaqueductal grey. Chronic morphine treatment increased the proportion of neurons displaying an increased potassium conductance in response to a selective DOR-agonist. There was a corresponding reduction in responsiveness of CeA neurons to a selective mu-opioid agonist. By combining retrograde labelling and live cell recording of CeA-periaqueductal grey projection neurons, we found nearly all (6/7 or 86%) projection neurons responded to delta agonist after chronic treatment with morphine versus only 2/7 neurons (29%) from vehicle-treated animals. Other physiological properties of amygdala neurons did not differ between neurons from vehicle and morphine-treated animals. Taken together, these results indicate that chronic treatment with morphine upregulates functional DORs in neurons projecting from the CeA to periaqueductal grey. CeA-periaqueductal grey projections form part of the descending antinociceptive and autonomic control systems suggesting an upregulation of functional DOR in antinociception, emotion and anxiety following chronic morphine treatment.