Contribution of glutamatergic systems in locus coeruleus to nucleus paragigantocellularis stimulation-evoked behavior

The role of extracellular glutamate, within the locus coeruleus, in mediati on of the behavioral signs elicited by electrical stimulation of the nucleu s paragigantocellularis (PGi) was investigated in conscious, opioid-naive r ats. Each rat was prepared with a chronically implanted unilateral electrod e within the PGi and a microdialysis guide cannula directed at the ipsilate ral locus coeruleus. Opioid withdrawal-like behaviors (rearing, teeth-chatt ering, wet-dog shakes, etc.) and increases in extracellular glutamate conce ntrations within the locus coeruleus were evoked, in a frequency-dependent (0.5-50 Hz) manner, during PGI stimulation. Reverse dialysis perfusion of t he locus coeruleus with the nonspecific glutamate receptor antagonist, kynu renic acid (0.1, 1 mM), reduced the intensity of stimulation-induced behavi ors by roughly 50%, but had no effect on the corresponding increases in glu tamate concentrations. Perfusion of the locus coeruleus with the glutamate transporter inhibitor, L-trans-pyyrolidine dicarboxylic acid, at 1, but not at 0.1, mM significantly increased glutamate levels in dialysates. Neither concentration of the transporter inhibitor altered the behavioral score. T he results indicate that the opioid withdrawal-like behaviors elicited by e lectrical stimulation of the brainstem at the site of the PGi are positivel y correlated with locus coeruleus levels of glutamate, and suggest further that the behaviors are partially mediated by release of glutamate within th e locus coeruleus or its immediate vicinity. (C) 1999 Elsevier Science Inc.