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.) infussions of morphine (26 nmol/1 μl/ht) of saline (1 μl/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 μl). 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 μM following 12 nmol/5 μl naloxone, and from 9.5 ± 1.9 to 20.5 ± 3.3 μM following 48 nmol/5 μl 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.
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