RT Journal Article
SR Electronic
T1 Increase in dopamine metabolites in rat brain by neurotensin.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1
OP 6
VO 223
IS 1
A1 E Widerlöv
A1 C D Kilts
A1 R B Mailman
A1 C B Nemeroff
A1 T J Mc Cown
A1 A J Prange, Jr
A1 G R Breese
YR 1982
UL http://jpet.aspetjournals.org/content/223/1/1.abstract
AB Neurotensin (NT), an endogenous tridecapeptide, is heterogeneously distributed in the central nervous system. The present study examined the effects of physiologically and behaviorally active doses of NT (1--100 micrograms intracisternally) on dopamine, serotonin and their primary metabolites as well as accumulation of dopa after inhibition of dopa decarboxylase. NT was shown to increase dopa accumulation when compared with saline treatment, suggesting that dopamine synthesis was increased. In accord with this view, 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). Interestingly, the increase in homovanillic acid was greater than that for dihydroxyphenylacetic acid. In striatum, an initial increase in dopamine content after 30 micrograms of NT was followed by an increase and a subsequent decrease of dopamine metabolites. Several other neuropeptides (Met-enkephalin, cholecystokinin-8, thyrotropin releasing hormone, substance P and d-Arg9-NT), at doses equimolar to 30 micrograms 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.