Behavioral and neurochemical correlates of morphine and hypoxia interactions

Decreased oxygen availability (hypoxia) impairs the synthesis of dopamine and serotonin in parallel with a decline in open-field behavior. If hypoxic-induced deficits in dopamine and serotonin metabolism are physiologically important, then stimulation of their synthesis may help reverse hypoxic-induced neurochemical and behavioral deficits. Acute morphine sulfate (50 mg/kg) increased dihydroxyphenylacetic acid/dopamine ratios (DOPAC/DA) (+20%), the conversion of [3H]tyrosine to [3H]dopamine (+73%) and open-field activity (+130%) in CD-1 male mice. However, morphine failed to significantly alter the incorporation of [3H]tryptophan to [3H]serotonin. Morphine antagonized the hypoxic-induced impairment of dopamine metabolism and locomotor activity. DOPAC/DA ratios of hypoxic animals that were treated with morphine were identical to controls, and conversion rates of [3H]tyrosine to [3H]dopamine were increased. Total distance in an automated activity monitor following the combination of morphine and hypoxia increased 79% compared to a 48% decrease with hypoxia alone. These results suggest that both hypoxia and morphine alter the dopaminergic system, but in opposite directions. These interactions may help to explain why morphine is able to ameliorate hypoxic-induced changes in behavior.