Neurotensin-induced antinociception and hypothermia in mice: antagonism by TRH and structural analogs of TRH |
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| Authors: | D E Hernandez C B Nemeroff M H Valderrama A J Prange |
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| Institution: | 1. Biological Sciences Research Center, University of North Carolina School of Medicine, Chapel Hill, NC 27514, U.S.A.;2. Department of Psychiatry, and the Neurobiology Program, University of North Carolina School of Medicine, Chapel Hill, NC 27514, U.S.A. |
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| Abstract: | Intracisternal (IC) administration of neurotensin (NT) in a dose of 10 micrograms produced a significant hypothermia and antinociception in the hot-plate test in mice. Both of these effects of IC NT were completely antagonized by concomitant administration of equimolar doses of thyrotropin-releasing hormone (TRH) and several TRH congeners including 3-methyl-His-TRH (pGlu-3-methyl-His-Pro-NH2), MK-771 (pyro-2-aminoadipyl-histidyl-thiazolidine-4-carboxamide), beta-ala-TRH (pGlu-His-Pro-beta-ala-NH2), and RX-77368 (pGlu-His-dimethyl-Pro-NH2). The antagonism by TRH and TRH analogs on NT-induced hypothermia and antinociception was dose-dependent. Of particular interest was the finding that RX-77368 not only blocked the effects of NT but also produced hyperalgesia. It appears that TRH analogs that are more resistant to biologic degradation are, like TRH, capable of blocking NT-induced behaviors. |
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| Keywords: | thyrotropin-releasing hormone neurotensin antinociception hypothermia |
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