title: Evidence for the involvement of excitatory amino acid pathways in the development of precipitated withdrawal from acute and chronic morphine: an in vivo voltammetric study in the rat locus coeruleus.
abstract: Previous studies have demonstrated that activation of excitatory amino acid (EAA) pathways projecting to the locus coeruleus may be involved in the increased firing of locus coeruleus (LC) neurons during opioid withdrawal. Using differential normal pulse voltammetry to monitor catechol oxidation current (CA.OC), an index of neuronal activity in the LC, the role of EAA pathways in naloxone precipitated withdrawal after acute and chronic morphine treatment was examined. Acute morphine treatment (10 micrograms i.c.v.) significantly reduced the CA.OC signal in the LC to 54.3 +/- 3.1% of baseline. Naloxone challenge (1 mg/kg i.v.) completely reversed the morphine effect and produced a significant increase in the CA.OC signal above baseline, peak 145.4 +/- 10.1% of baseline. This naloxone-induced rebound response was attenuated by pretreatment with the EAA receptor antagonists gamma-D-glutamylglycine (DGG) (2, 20, 200 micrograms i.c.v.) and (-)-2-amino-7-phosphonoheptanoic acid (D-APH), but not L-APH (25 micrograms i.c.v.). In chronically morphine-treated rats (25 micrograms/h i.c.v., 5 days), naloxone challenge (1 mg/kg i.v.) produced a significant increase in CA.OC signal, peak 466.5 +/- 112.7% of baseline. This naloxone-induced response was attenuated by pretreatment with DGG (200 micrograms i.c.v.) or D-APH (25 micrograms i.c.v.). To the extent that CA.OC reflects locus coeruleus neuronal activity, the present findings further suggest that increases in locus coeruleus activity during naloxone precipitated withdrawal after both acute and chronic morphine treatment are mediated at least in part by activation of EAA pathways.
authors.affiliation: Department of Pharmacology and Toxicology, Queen's University, Kingston, Ont., Canada.
authors.forename: M
authors.initials: M
authors.lastname: Hong
authors.forename: B
authors.initials: B
authors.lastname: Milne
authors.forename: K
authors.initials: K
authors.lastname: Jhamandas
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists; D007263:Infusions, Parenteral; D007276:Injections, Intraventricular; D008125:Locus Coeruleus / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009021:Morphine Dependence / Q000503:physiopathology*; D009270:Naloxone / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011199:Potentiometry / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000502:physiology*; D013237:Stereoisomerism; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
chemical_list: D000596:Amino Acids; D004151:Dipeptides; D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; C028929:gamma-glutamylglycine; D009270:Naloxone; D015763:2-Amino-5-phosphonovalerate; D009020:Morphine; C031231:2-amino-7-phosphonoheptanoic acid