The Effects of Discontinuous Morphine Intoxication on the Pools of Neuroactive Amino Acids and Biogenic Amines in Brain Regions

Abstract

We developed a model of discontinuous morphine intoxication, which is based on 1, 2, and 3 cycles of intraperitoneal morphine administration to rats. During cycle 1, morphine was injected at a dose of 30 mg/kg twice a day for 4 days; a dose of 40 mg/kg was used in cycles 2 and 3. These periods were alternated with drag-free periods. We studied the effects of intermittent morphine administration on the levels of biogenic amines, including serotonin, dopamine, and norepinephrine, and their metabolites and several neuroactive amino acids in the cerebral cortex and midbrain of rats. The alterations in the indices of the serotonergic neurotransmitter system and the pool of free amino acids in brain regions varied depending on the duration of discontinuous morphine administration. Discontinuous morphine intoxication for 14 days was accompanied by the accumulation of serotonin and its metabolites in both brain regions that were studied. This effect became less expressed after more prolonged morphine administration. The metabolic effects of 21-daylong discontinuous morphine intoxication were reflected in the lower content of amino acids and pools of aromatic, neurotransmitter, and excitatory amino acids. Under these conditions, the levels of bio¬genic amines and their metabolites changed insignificantly