Noradrenaline release in rat locus coeruleus is regulated by both opioid and alpha(2) -adrenoceptors

Extracellular fluid levels of noradrenaline (NA) in the locus coeruleus (LC) during naloxone-precipitated morphine withdrawal with pretreatment of yohimbine (1 mg kg (-1), s.c.) or clonidine (1 mg kg (-1), s.c.) were measured in rats. There was a significant increase in the NA level after the injection of naloxone (2 mg kg (-1), i.p.) in the morphine-dependent rats. Moreover, the NA levels in the LC markedly increased during the 30-60 min following the naloxone (i.p.) challenge in the morphine-dependent rats pretreated with yohimbine. In contrast, the naloxone challenge in morphine-dependent rats pretreated with clonidine notably decreased the levels of NA in the LC. Behavioral signs of withdrawal were observed following the naloxone challenge in the morphine-dependent rats pretreated with yohimbine, with minimal signs in the morphine-infused rats pretreated with clonidine, and none in the saline-infused controls. These results directly suggest that NA increased within the LC after the naloxone challenge in morphine-dependent animals pretreated with yohimbine may be, at least in part, regulated by alpha(2) -adrenoceptors in the LC.