Effect of selective inhibitors of tyrosine and tryptophan hydroxylases on self-stimulation in the rat

Measurement of amine levels suggested that catecholamine depletion was more influential at increasing the self-timulation threshold than serotonin depletion, and data suggest that both catecholicamines and serotonin are involved in pathways for self-stimulating drive-reward.

Abstract

The effect of various drugs on self-stimulation of rats having electrodes implanted in the medial forebrain bundle was measured. An increase in threshold for self-stimulation was observed in most rats following administration of: reserpine, 0.3 and 0.5 mg/kg; l-α-methyl-p-tyrosine, 100 mg/kg; dl-α-methyl-p-tyrosine, 200 mg/kg; dl-5-bromotryptophan, 290 mg/kg; dl-p-chlorophenylalanine, 150 and 200 mg/kg; and dl-6-fluorotryptophan, 150 mg/kg. Reserpine, a depletor of both catecholamines and serotonin, was the most effective agent at increasing the threshold. This was followed by the tyrosine hydroxylase inhibitors α-methyl-p-tyrosine and dl-5-bromotryptopha. At the doses used, the tryptophan hydroxylase inhibitors dl-p-chlorophenylalanine and dl-6-fluorotryptophan were less effective. In general, the maximum effects of the drugs corresponded in time with the maximum depletion of the various amines. Measurement of amine levels suggested that catecholamine depletion was more influential at increasing the self-timulation threshold than serotonin depletion. Reserpine, which depletes all amines, seemed to have a larger effect on self-stimulation than would be indicated by the drop in amine levels. Over-all, the data suggest that both catecholamines and serotonin are involved in pathways for self-stimulating drive-reward with the catecholamines being more influential.