Excitatory amino acids and morphine withdrawal: differential effects of central and peripheral kynurenic acid administration.

The non-selective excitatory amino acid antagonist kynurenic acid, which does not readily cross the blood-brain barrier, dose-dependently attenuated the behavioral signs of naltrexone-precipitated withdrawal in morphine-dependent rats following both intraventricular and subcutaneous administration. However, intraventricular and subcutaneous administration of kynurenic acid had different effects on individual withdrawal behaviors. Moreover, single unit recordings in anesthetized animals showed that intraventricular, but not subcutaneous, kynurenic acid administration attenuated the withdrawal-induced increased firing of locus coeruleus neurons. These studies indicate that: (1) both central and peripheral excitatory amino acid receptors may play an important role in opiate withdrawal; and (2) excitatory amino acid antagonist treatments might be developed to reduce opiate abstinence symptoms in man.