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Hypothermia induced by the putative 5-HT1A agonists LY165163 and 8-OH-DPAT is not prevented by 5-HT depletion

P H Hutson1, T P Donohoe, G Curzon

  • 1Department of Neurochemistry, Institute of Neurology, London, U.K.

European Journal of Pharmacology
|November 10, 1987
PubMed

Insights

The serotonin 5-HT1A agonist LY165163 induces hypothermia in rats, an effect likely mediated by postsynaptic receptors rather than presynaptic serotonin stores.

Area of Science:

  • Neuropharmacology
  • Serotonin receptor research

Background:

  • The serotonin 5-HT1A receptor is a key target for understanding thermoregulation.
  • Investigating the mechanism of action for novel 5-HT1A agonists is crucial for drug development.

Purpose of the Study:

  • To investigate the hypothermic effects of the putative 5-HT1A agonist LY165163 in rats.
  • To determine if the hypothermia induced by LY165163 is dependent on presynaptic serotonin (5-HT) stores.

Main Methods:

  • Administered LY165163 and 8-OH-DPAT (a known 5-HT1A agonist) subcutaneously to rats.
  • Depleted brain serotonin levels using p-chlorophenylalanine (pCPA) or intraventricular 5,7-dihydroxytryptamine (5,7-DHT).
  • Measured body temperature changes and analyzed the effects of serotonin depletion on drug-induced hypothermia.

Main Results:

  • LY165163 caused a significant, dose-dependent hypothermia in rats.
  • Serotonin depletion via pCPA or 5,7-DHT significantly enhanced the hypothermic effects of both LY165163 and 8-OH-DPAT.
  • The hypothermia induced by these agonists was not dependent on presynaptic 5-HT stores.

Conclusions:

  • The hypothermia induced by LY165163 and 8-OH-DPAT in rats is likely mediated by postsynaptic 5-HT1A receptors.
  • Presynaptic serotonin availability does not appear to be essential for the hypothermic response to these agonists.

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