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Adult awake rats which received neonatal pargyline and 5,7-dihydroxytryptamine to severely reduce CNS serotonin terminals and perikarya have a reduced rate of accumulation of brain stem 5-hydroxytryptophan after Ro-44602. The rate of accumulation in the cerebral cortex and spinal cord were near normal when adult, even though serotonin and 5-hydroxyindoleacetic acid were sharply reduced in these regions. The respiratory response to 5-methoxy N,N-dimethyl-tryptamine was much more pronounced in pargyline-5,7-dihydroxytryptamine treated rats than in controls. If supersensitivity in serotonin receptors only develops in areas with decreased transmitter turnover, the site of action of serotonin agonists to depress respiration would seem to reside in the brain stem region. The results also suggest that compensatory changes in turnover do not develop to a similar degree in all CNS areas with altered serotonin content.
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