No abstract

The specific narcotic antagonist naloxone (0.4 milligram) was given intravenously to seven chronic schizophrenics who reported that they had very frequent auditory hallucinations. Saline solution was used as a placebo. The coded study did not reveal any effect of naloxone on hallucinations or on global psychopathology.

Cyclic AMP and dibutyryl‐cyclic AMP, a derivative of cyclic AMP resistant to phosphodiesterase inactivation, were injected into the lateral ventricles of rats. These nucleotides did not change the level of brain 5‐HT but increased the brain level of its principal metabolite, 5‐hydroxyindoleacetic acid. Cyclic AMP was less potent than dibutyryl‐cyclic AMP. Butyrate and 5′‐AMP were inactive. The effect of dibutyryl cyclic AMP on 5‐HT metabolism was studied both in vivo and in vitro. The rate of synthesis of 5‐HT was measured by the rate of accumulation of 5‐hydroxyindoleacetic acid after the transport of this acid out of the brain was blocked with probenecid. The rate of synthesis of brain 5‐HT increased from 0‐38 μg/g/h in control rats to 0‐65 μg/g/h after dibutyryl‐cyclic AMP. In addition cyclic AMP and dibutyryl‐cyclic AMP markedly increased brain tryptophan, while AMP was inactive. Since brain tryptophan hydroxylase has a Km for its substrate that is much higher than the concentrations of tryptophan normally present in the brain, it is likely that the increase in the rate of synthesis of brain 5‐HT is secondary to the cyclic AMP induced increase in the levels of brain tryptophan. In vitro studies revealed that dibutyryl‐cyclic AMP increased the uptake of radioactive labelled tryptophan into slices of rat brain stem and the formation of 5‐HT and 5‐hydroxyindoleacetic acid.