The nucleus paragigantocellularis and opioid withdrawal-like behavior

Participation of the nucleus paragigantocellularis (PGi) in mediation of op ioid withdrawal was examined in conscious, unrestrained, non-opioid-depende nt rats, using electrical stimulation of the PGI. A characteristic series o f behaviors, which resembled those seen during naloxone-precipitated withdr awal from dependence on the opioid agonist, butorphanol, was elicited durin g 30 min of PGI stimulation. Thus, the behavioral syndrome has been termed opioid withdrawal-like. Simultaneous microdialysis measurement of glutamate within the locus ceruleus indicated a positive correlation between extrace llular glutamate concentrations and behavioral responses. Behavioral respon ses were inhibited by 50% during reverse dialysis perfusion of the locus ce ruleus with the glutamate receptor antagonist, kynurenic acid, without any effect on glutamate concentrations. Thus, increases in locus ceruleus gluta mate partially mediate opioid withdrawal-like behavior. Intracerebroventric ular (i.c.v.) injections of the opioid antagonist, naloxone, or of the mu-s elective (beta-funaltrexamine) or the delta-selective (naltrindole) opioid antagonists decreased, but did not abolish, stimulation-induced behavioral responses. Similar i.c.v. injections of the kappa-selective antagonist, nor -binal-torphimine, had no effect on behavioral responses to PGI stimulation . Activation of the PGI by electrical stimulation can elicit behaviors simi lar to those observed during opioid withdrawal. Moreover, additional levels of complexity are evident in the neuropharmacology of PGI stimulation-indu ced opioid withdrawal-like behavior. Copyright (C) 2000 National Science Co uncil, ROC and S. Karger AG, Basel.