Electrical stimulation of nucleus paragigantocellularis induces opioid withdrawal-like behaviors in the rat

To examine a role for the medullary nucleus paragigantocellularis (PGi) in mediation of the symptomatology of opioid withdrawal, bilateral electrical stimulation of the PGi was performed in conscious, unrestrained, opioid nai ve (nondependent) rats. A characteristic series of behaviors was elicited d uring each 30-min session of PGi stimulation. The profile of these behavior s resembled qualitatively, but was not quantitatively identical with those seen during precipitated withdrawal from opioid dependence. This behavioral syndrome has been termed, opioid withdrawal-like behavior. The opioid with drawal-like behaviors were voltage-, but not frequency-, dependent. Toleran ce to repeated stimulation of the PGi did not develop following a series of 30-min runs of stimulation over 3.5 h. Intracerebroventricular (ICV) injec tions of the nonselective opioid antagonist, naloxone, significantly decrea sed (by 40-50%) the intensity of stimulation-induced behavioral responses, as did injections of either the mu-selective (beta-funaltrexamine, beta-FNA ) or the delta-selective (naltrindole, NTI) opioid antagonists. In contrast , similar ICV injections of the kappa-selective antagonist, nor-binaltorphi mine (nor-BNI), did not block behavioral responses to PGi stimulation. The results indicate that activation of the PGI by electrical stimulation can e licit behaviors similar to those observed during opioid withdrawal. Endogen ous opioids, acting through mu- and delta-, but not kappa-opioid receptors, participate in mediating opioid withdrawal-like behaviors induced by PGi s timulation. (C) 1999 Elsevier Science Inc.