The effects of p-chlorophenylalanine (PCPA) treatment on the substance P content measured in discrete brain nuclei of normal and neonatally-induced hypothyroid rats.

Neonatal hypothyroidism is known to induce the accumulation of substance P and serotonin in many discrete brain nuclei of the rat. In this work, we have studied the effects of p-chlorophenylalanine (PCPA), a serotonin (5-HT) depleting drug, on the regional distribution of substance P in the brains of neonatally-induced hypothyroid and euthyroid rats. PCPA injections were given 48 and 24 h before sacrifice and the peptide content of discrete brain nuclei, removed by punches of frozen brain slices, was measured by radioimmunoassay. In hypothyroid animals, substance P levels were significantly increased in the n. paraventricularis, n. medialis thalami, n. arcuatus. n. mamillaris medialis, substantia nigra, area ventralis tegmenti, n. interpeduncularis, substantia grisea and n. dorsalis raphes. This hypothyroid-induced accumulation of substance P was completely abolished, and even reversed in some nuclei, by PCPA treatment. Interestingly, in normal rats, following PCPA treatment, the substance P level was increased in n. paraventricularis pars magnocellularis, n. ventromedialis (hypothalami), n. dorsomedialis pars dorsalis (hypothalami), n. amygdaloideus centralis, area ventralis tegmenti, substantia grisea, n. medianus raphes and n. dorsalis raphes. These results lend support to the existence of a physiological relationship between both substance P and serotonergic systems.