These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Brainstem 5-hydroxytrytamine1A binding sites are not down-regulated by agonists which induce tolerance in the rat: myoclonus and other serotonergic behaviors.
    Author: Murthy JN, Pranzatelli MR.
    Journal: J Recept Res; 1992; 12(3):287-97. PubMed ID: 1387164.
    Abstract:
    To study the regulation of 5-HT1A receptors in the brainstem, the region most relevant to the serotonin syndrome and to serotonin-responsive human myoclonic disorders, we chronically treated rats with various 5-HT1A agonists and labeled 5-HT1A sites with [3H]8-OH-DPAT. Daily injection for 30 consecutive days of 10 mg/kg ip 8-OH-DPAT (pre- and post-synaptic 5-HT1A agonist) significantly decreased 8-OH-DPAT-evoked flat body posture, forelimb myoclonus, and hypothermia compared to chronic vehicle injection. There was no cross tolerance to 8-OH-DPAT in rats chronically injected with ipsapirone or buspirone (presynaptic 5-HT1A agonists). However, none of the 5HT1A agonists significantly altered Bmax of brainstem 5-HT1A binding sites. Chronic injection with other drugs such as 1-propranolol, (+/-) pindolol and spiperone (5-HT1A and 5-HT2 antagonists), methysergide (5-HT1 and 5-HT2 antagonist), and agonists and antagonists at various other 5-HT receptors also had no effect on binding parameters. These data demonstrate lack of cross-tolerance between pre- and post-synaptically acting 5-HT1A agonists and absence of down-regulation of presynaptic 5-HT1A sites at doses which induced tolerance of 5-HT1A-mediated behaviors of the serotonin syndrome. They suggest changes in the post-synaptic cell rather than the receptor recognition site as the mechanism of tolerance.
    [Abstract] [Full Text] [Related] [New Search]