Effect of p-chlorophenylalanine at moderate dosage on 5-HT and 5-HIAA concentrations in brain regions of control and p-chloroamphetamine treated rats

Abstract

The effects of p-chlorophenylalanine (PCPA, 100–150 mg/kg × 1, i.p.), doses which decrease brain 5-hydroxytryptamine (5-HT) by 30–50%, were investigated in both intact rats and 14 days after giving p-chloroamphetamine (PCA, 10 mg/kg/day × 2, i.p.). The PCPA dose-dependently decreased brain regional 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) 24 hr later. As per cent decreases of 5-HIAA were greater than those of 5-HT in cortex, striatum and hippocampus 5-HIAA/5-HT ratios fell, suggesting that partial inhibition of 5-HT synthesis by PCPA increases 5-HT conservation in these terminal regions. In the hypothalamus and brain stem, decreases of the ratio were small or absent. The PCA given without subsequent PCPA treatment decreased 5-HT and 5-HIAA so that 5-HT fell by about 70% in the cortex, striatum and hippocampus, 55% in the brain stem but only by 27% in the hypothalamus. The PCPA given after PCA decreased 5-HT and 5-HIAA further but not the 5-HIAA/5-HT ratios and increased the ratio in the brain stem. The 5-HIAA/5-HT findings imply that the increase of 5-HT conservation after PCPA treatment does not occur after partial depletion of 5-HT by PCA. The increase of the 5-HIAA/5-HT ratio in the brain stem is explicable by the resistance to both PCA and PCPA of 5-HT in cell bodies where the ratio is high. Results are discussed in relation to the question of whether the PCA treatment used destroys axon terminals projecting from the dorsal but not from the median raphe.