Contribution of glutamatergic systems in locus coeruleus to nucleus paragigantocellularis stimulation-evoked behavior.
The role of extracellular glutamate, within the locus coeruleus, in mediation of the behavioral signs elicited by electrical stimulation of the nucleus paragigantocellularis (PGi) was investigated in conscious, opioid-naive rats. Each rat was prepared with a chronically implanted unilateral electrode within the PGi and a microdialysis guide cannula directed at the ipsilateral locus coeruleus. Opioid withdrawal-like behaviors (rearing, teeth-chattering, wet-dog shakes, etc.) and increases in extracellular glutamate concentrations within the locus coeruleus were evoked, in a frequency-dependent (0.5-50 Hz) manner, during PGi stimulation. Reverse dialysis perfusion of the locus coeruleus with the nonspecific glutamate receptor antagonist, kynurenic acid (0.1, 1 mM), reduced the intensity of stimulation-induced behaviors by roughly 50%, but had no effect on the corresponding increases in glutamate concentrations. Perfusion of the locus coeruleus with the glutamate transporter inhibitor, L-trans-pyrrolidine 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. The results indicate that the opioid withdrawal-like behaviors elicited by electrical stimulation of the brainstem at the site of the PGi are positively correlated with locus coeruleus levels of glutamate, and suggest further that the behaviors are partially mediated by release of glutamate within the locus coeruleus or its immediate vicinity.
Liu
N
N
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39215-4505, USA.
Ho
I K
IK
Rockhold
R W
RW
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001479:Basal Ganglia / Q000033:anatomy & histology / Q000378:metabolism / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology*; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology*; D007736:Kynurenic Acid / Q000494:pharmacology; D008125:Locus Coeruleus / Q000033:anatomy & histology / Q000378:metabolism / Q000502:physiology*; D008297:Male; D017551:Microdialysis; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013238:Stereotaxic Techniques; D013239:Stereotyped Behavior / Q000187:drug effects
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D003998:Dicarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D014179:Neurotransmitter Uptake Inhibitors; D011759:Pyrrolidines; D018698:Glutamic Acid; C083486:pyrrolidine-2,4-dicarboxylic acid; D007736:Kynurenic Acid