Behavior of monkeys during opiate withdrawal and locus coeruleus stimulation

The noradrenergic nucleus locus coeruleus (LC) has been implicated in morphine withdrawal. The behavioral effects of opiate antagonist-precipitated morphine withdrawal in chair-restrained Macaca arctoides were therefore compared with LC electrical field stimulation. Both continuous LC stimulation and administration of low doses of naloxone to morphine pellet implanted monkeys produced a significant increase in the same group of behaviors reported previously to follow activation of the LC, without significant increases in general activity or distress behaviors. Signs of autonomic hyperactivity and distress were observed at high doses of naloxone, but not during LC stimulation. Monkeys which had not received morphine treatment did not specifically increased during low intensity LC stimulation is also selectively increased during naloxone-precipitated morphine withdrawal. These data are consistent with and suggest a behavioral consequence of the interactions of opioids with the LC reported at the molecular, intracellular, and cellular level.