title: Naloxone-precipitated morphine withdrawal increases pontine glutamate levels in the rat.
abstract: Extracellular fluid (ECF) levels of glutamate (Glu) and aspartate (Asp) were measured in the locus coeruleus (LC) during morphine withdrawal by using microdialysis in conscious morphine-dependent Sprague-Dawley rats. Guide cannulae were implanted chronically and rats were given intracerebroventricular (i.c.v.) infusions of morphine (26 nmol/1 microliters/hr) or saline (1 microliters/hr) for 3 days. Microdialysis probes (2 mm tip) were inserted into the LC 24 hr before precipitation of withdrawal by i.c.v. injection of naloxone (12 or 48 nmol/5 microliters). Behavioral evidence of withdrawal (teeth-chattering, wet-dog shakes, etc.) was detected following naloxone challenge in morphine, but not in saline-infused rats. Increases (P < 0.01) in ECF levels of Glu (and Asp, to a lesser degree) were noted after naloxone-precipitated withdrawal only in the morphine group. The ECF Glu levels in the LC increased from 9.6 +/- 2.7 to 15.5 +/- 5.0 microM following 12 nmol/5 microliters naloxone, and from 9.5 +/- 1.9 to 20.5 +/- 3.3 microM following 48 nmol/5 microliters naloxone, before and in the first 15 min sample after the precipitation of withdrawal in the morphine-dependent rats, respectively. These results provide direct evidence to support the role of excitatory amino acids within the LC in morphine withdrawal.
authors.affiliation: Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson 39216-4505.
authors.forename: T
authors.initials: T
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
authors.forename: R W
authors.initials: RW
authors.lastname: Rockhold
authors.forename: I K
authors.initials: IK
authors.lastname: Ho
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D003956:Dialysis / Q000379:methods; D004347:Drug Interactions; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D009270:Naloxone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
chemical_list: D005971:Glutamates; D001224:Aspartic Acid; D009270:Naloxone; D018698:Glutamic Acid; D009020:Morphine