Comparison of relative potencies of i.V. And i.C.V. Administered 8-OH-DPAT gives evidence of different sites of action for hypothermia, lower lip retraction and tail flicks

Gyorgy Bagdy, C. Thang To

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)-induced temperature reduction, lower lip retraction and tail flick responses are widely used models of 5-HT(1A) receptor function. To obtain information about the sites of receptors mediating these effects we measured these responses, parallel over wide dose ranges after intracerebroventricular (i.c.v., 0.6-67 μg/kg) and intravenous (i.v., 3-500 μg/kg) administration. Analysis of the dose-response curves provided evidence for a 9.8-fold ratio of the potency of 8-OH-DPAT following i.c.v. compared to i.v. administration on body temperature reduction (ED50 values are 5.1 and 50 μg/kg, after i.c.v. and i.v. administration, respectively) and a 2.9-fold ratio in potency for lower lip retraction (ED50 values are 29 and 86 μg/kg, after i.c.v. and i.v. administration, respectively). 8-OH-DPAT was less potent in the induction of tail flicks than of the other responses and had a lower potency after i.c.v. than after i.v. administration (ED50 values, the first one extrapolated, are 526 and 246 μg/kg, after i.c.v. and i.v. administration, respectively). In addition, the i.c.v. ED50 for temperature reduction was significantly lower than those for lower lip retraction or tail flick responses. The relative potency, that is, the ratio of i.v. and i.c.v. ED50, was significantly higher for temperature reduction than for lower lip retraction or tail flick responses (ED50 i.v./ED50 i.c.v. values are 9.8, 2.9, and 0.47, respectively). These data provide evidence that distinct sites of action are involved in these models. Temperature reduction is mediated mainly by postsynaptic receptors in the close vicinity of the lateral ventricle. Receptors that mediate lower lip retraction are located more distantly in the brain, supporting previous evidence that they are somatodendritic autoreceptors, and receptors in the spinal cord are probably responsible for tail flick responses.

Original languageEnglish
Pages (from-to)53-58
Number of pages6
JournalEuropean Journal of Pharmacology
Volume323
Issue number1
DOIs
Publication statusPublished - Mar 26 1997

Keywords

  • 5-HT (5-hydroxytryptamine, serotonin)
  • 5-HT(1A) receptor
  • 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin)
  • Behavior
  • Body temperature
  • Intracerebroventricular administration
  • Lower lip retraction
  • Tail flick

ASJC Scopus subject areas

  • Pharmacology

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