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      Elevation of Serum Corticosterone in Rats by Dopamine Agonists Related in Structure to Pergolide

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          Abstract

          Two chemical analogs of pergolide were examined to test further the idea that pergolide elevates serum corticosterone concentration in rats by activation of brain dopaminergic receptors. LY116467, which contains an N-methyl substituent in place of the N-n-propyl substituent in pergolide, was less potent than pergolide in lowering brain levels of 3,4-dihydroxyphenylacetic acid (Dopac), the metabolite of dopamine. LY 116467 increased serum corticosterone concentration in rats at a dose of 3 mg/kg (a higher dose than is required for pergolide), and the effect was prevented by spiperone pretreatment. LY141865, which has been reported to differ from pergolide in not activating dopamine-sensitive adenylate cyclase and which was found in this study to have much less affinity for serotonin receptors than does pergolide, increased serum corticosterone in much the same manner as pergolide, only slightly higher doses being required. The effect of LY141865 was prevented by pretreatment with haloperidol but not domperidone. Both haloperidol and domperidone increased serum prolactin concentration when given alone or in combination with LY141865, indicating they were both capable of blocking peripheral (pituitary) dopamine receptors. In contrast, haloperidol but not domperidone caused a marked elevation in brain levels of Dopac and of homovanillic acid and prevented the lowering of these brain dopamine metabolites by LY141865. The ability of LY141865 to increase serum corticosterone concentration was attenuated in rats that had received four daily injections of pergolide mesylate, indicating cross-tolerance had occurred. These results strengthen the hypothesis that activation of brain dopaminergic receptors leads to increased serum corticosterone concentration in rats.

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          Author and article information

          Journal
          NEN
          Neuroendocrinology
          10.1159/issn.0028-3835
          Neuroendocrinology
          S. Karger AG
          0028-3835
          1423-0194
          1983
          1983
          26 March 2008
          : 36
          : 4
          : 285-290
          Affiliations
          Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Ind., USA
          Article
          123469 Neuroendocrinology 1983;36:285–290
          10.1159/000123469
          6866215
          © 1983 S. Karger AG, Basel

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          Page count
          Pages: 6
          Categories
          Original Paper

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