ACTIVATION OF COERULEOSPINAL NORADRENERGIC INHIBITORY CONTROLS DURINGWITHDRAWAL FROM MORPHINE IN THE RAT

We previously reported that withdrawal from morphine induces the expre ssion of Fos, a marker of neuronal activity, in spinal cord neurons, p articularly in laminae I and II of the superficial dorsal horn, and th at the magnitude of Fos expression is increased in rats with a midthor acic spinal transection. We suggested that loss of withdrawal-associat ed increases in descending inhibitory controls that arise in the brain stem underlie the increased Fos expression after spinal transection. H ere, we addressed the origin of the supraspinal inhibition. We injecte d rats intracerebroventricularly with saline or anti-dopamine-beta-hyd roxylase-saporin, a toxin that destroys noradrenergic neurons of the l ocus coeruleus. Eleven days later, we implanted rats with morphine or placebo pellets, and after 4 d, we precipitated withdrawal with naltre xone. One hour later, the rats were killed, their brains and spinal co rds were removed, and transverse sections of the brains and spinal cor ds were immunoreacted with an antibody to Fos. In placebo-pelleted rat s, the toxin injection did not alter behavior and did not induce expre ssion of the Fos protein. However, compared with saline-injected withd rawing rats, the toxin-treated rats that underwent withdrawal demonstr ated an intense withdrawal behavior rarely seen in the absence of toxi n, namely forepaw fluttering. The rats also had significantly increase d Fos-like immunoreactivity in all laminae of the cervical cord and in laminae I and II and the ventral horn of the lumbar cord. No differen ces were recorded in the sacral cord. We conclude that the effects of spinal transection in rats that withdraw from morphine in part reflect a loss of coeruleospinal noradrenergic inhibitory controls.