EFFECTS OF ANTIDEPRESSANT DRUG-TREATMENT ON LEVELS OF NPY OR PREPRO-NPY-MESSENGER RNA IN THE RAT-BRAIN

The effects of acute and chronic treatment with the tricyclic antidepressant drugs, imipramine, clomipramine and desipramine on levels of neuropeptide Y (NPY) and prepro-NPY-mRNA were studied in different areas of the rat brain. Chronic treatment with imipramine (6.3-25 mg/kg/day) for 10-30 days caused an approx. 15-25% reduction in NPY immunoreactivity in the frontal cortex, but only insignificant changes in striatum, hippocampus, amygdala and hypothalamus. Slight and insignificant changes in the concentrations of prepro-NPY-mRNA were also detected by Northern blot analysis in these brain areas. Only in the hypothalamus was a 20% increase in prepro-NPY-mRNA found. NPY or prepro-NPY-mRNA levels were not altered 3 or 24 h after a single injection of imipramine. The effects of clomipramine and desipramine, at doses of 25 mg/kg daily for 10 days, were investigated in the frontal cortex and in the hippocampus. Except for a slight decrease in prepro-NPY-mRNA in the frontal cortex after desipramine no significant changes in NPY tissue levels or prepro-NPY-mRNA concentrations were observed in the frontal cortex and the hippocampus. In summary, treatment with the three tricyclic antidepressant drugs had no consistent effects on the brain NPY system. These data do not support the previous suggestion that antidepressant drugs may exert their actions by increasing NPY levels in the brain.