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Evidence that m-chlorophenylpiperazine-induced hyperthermia in rats is mediated by stimulation of 5-HT2C receptors

P Mazzola-Pomietto1, C S Aulakh, K M Wozniak

  • 1Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1264, USA.

Psychopharmacology
|February 1, 1996
PubMed

Insights

m-chlorophenylpiperazine (m-CPP) causes hyperthermia in rats, primarily through 5-HT2C receptor stimulation. This effect is blocked by specific antagonists, indicating a selective serotonin receptor mechanism.

Area of Science:

  • Pharmacology
  • Neuroscience
  • Serotonin Receptor Research

Background:

  • m-chlorophenylpiperazine (m-CPP) is a drug known to affect serotonin pathways.
  • Hyperthermia is a complex physiological response that can be influenced by various neurotransmitters.
  • Understanding the specific receptors involved in drug-induced hyperthermia is crucial for pharmacology.

Purpose of the Study:

  • To investigate the specific serotonin receptor subtype(s) responsible for m-CPP-induced hyperthermia in Wistar rats.
  • To determine if tolerance develops to the hyperthermic effects of m-CPP and if cross-tolerance occurs with other agonists.
  • To compare the hyperthermic response to m-CPP in different rat strains.

Main Methods:

  • Administration of m-CPP to Wistar rats and observation of body temperature changes.
  • Pretreatment with various receptor antagonists (5-HT1, 5-HT2, 5-HT3, alpha 2-noradrenergic, beta-adrenergic) to identify blocking agents.
  • Assessment of tolerance development through daily m-CPP administration and cross-tolerance studies with DOI.
  • Comparison of m-CPP effects in Wistar rats versus Fawn-Hooded (FH) rats.

Main Results:

  • m-CPP induced hyperthermia, peaking at 30 minutes.
  • Low doses of 5-HT1/5-HT2 and 5-HT2C/5-HT2A antagonists (metergoline, mesulergine, mianserin) blocked the hyperthermic effect.
  • High doses of 5-HT2A/5-HT2C antagonists (ketanserin, LY-53857, ritanserin) and a 5-HT1A/5-HT2A/D2 antagonist (spiperone) also attenuated the response.
  • No attenuation was observed with 5-HT3 antagonists (MDL-72222, ondansetron) or beta/alpha-adrenergic antagonists (propranolol, yohimbine).
  • Complete tolerance to m-CPP hyperthermia developed by day 5, with no cross-tolerance to DOI.
  • FH rats showed a significantly reduced hyperthermic response compared to Wistar rats.

Conclusions:

  • The findings strongly suggest that m-CPP-induced hyperthermia in rats is primarily mediated by the selective stimulation of serotonin 5-HT2C receptors.
  • Tolerance develops to m-CPP hyperthermia, but this is not associated with cross-tolerance to 5-HT2A receptor agonists.
  • Differences in response between rat strains highlight the role of genetic factors in 5-HT2C receptor-mediated effects.

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