INCREASE IN DOPAMINE METABOLITES IN RAT-BRAIN BY NEUROTENSIN

Abstract

Neurotensin (NT), an endogenous tridecapeptide, is heterogeneously distributed in the CNS. The effects of physiologically and behaviorally active doses of NT (1-100 .mu.g intracisternally) on dopamine, serotonin and their primary metabolites as well as accumulation of dopa after inhibition of dopa decarboxylase were examined. NT increased dopa accumulation when compared with saline treatment, suggesting that dopamine synthesis was increased. NT also caused a dose-dependent increase in homovanillic acid and dihydroxyphenylacetic acid, the major metabolites of dopamine, in several brain areas (striatum, olfactory tubercles, nucleus accumbens, frontal cortex and hypothalamus). The increase in homovanillic acid was greater than that for dihydroxyphenylacetic acid. In striatum, an initial increase in dopamine content after 30 .mu.g of NT was followed by an increase and a subsequent decrease of dopamine metabolites. Several other neuropeptides (Met-enkephalin, cholecystokinin-8, TRH, substance P and d-Arg9-NT), at doses equimolar to 30 .mu.g of NT, did not affect dopamine metabolites, whereas certain others (.beta.-endorphin and bombesin) increased their concentration in some brain areas. Except for the highest dose of NT, measures of serotonergic function were not affected by NT or any of the other neuropeptides.