Alterations in brain dopamine and serotonin metabolism during the development of tolerance to human beta-endorphin in rats.

Repeated intracisternal injections of human beta-endorphin lead to development of tolerance with respect to the catalepsy, analgesia, and hypothermia which are seen following a single injection. The initial injection of beta-endorphin results in increases in the dopamine metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in neostriatum, as well as increases in the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in hypothalamus and brainstem and a decrease in 5-HIAA in hippocampus. In the present study, we report changes in metabolism of dopamine and serotonin in specific brain areas during the development of tolerance to beta-endorphin. Thus, the development of tolerance to beta-endorphin with respect to catalepsy, analgesia, and hypothermia may be mediated by development of tolerance to the effects of beta-endorphin on brain dopamine and serotonin release.