Psychopharmacology

, Volume 130, Issue 2, pp 144–151

Functional subsensitivity of 5-HT2A and 5-HT2C receptors mediating hyperthermia following acute and chronic treatment with 5-HT2A/2C receptor antagonists

  • P. Mazzola-Pomietto
  • Charanjit S. Aulakh
  • Teresa Tolliver
  • Dennis L. Murphy
ORIGINAL INVESTIGATION

DOI: 10.1007/s002130050222

Cite this article as:
Mazzola-Pomietto, P., Aulakh, C., Tolliver, T. et al. Psychopharmacology (1997) 130: 144. doi:10.1007/s002130050222

Abstract

 In the present study, we investigated the duration of attenuation of the temperature increases produced by (±) 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and m-chlorophenylpiperazine (m-CPP) which followed pretreatment with four serotonin (5-HT) antagonists; metergoline, mesulergine, mianserin and ritanserin. The duration of attenuation of m-CPP-induced hyperthermia lasted less than 1 day for ritanserin, more than 1 day for the 5 mg/kg doses of both mianserin and metergoline and more than 2 days for the 5 mg/kg dose of mesulergine. The duration of attenuation of DOI-induced hyperthermia lasted less than 1 day for ritanserin, more than 1 day for mianserin, more than 2 days for the 5 mg/kg dose of metergoline and more than 4 days for mesulergine. Daily administration of a low (1.0 mg/kg per day) dose of ritanserin for 14 days led to an attenuation of the temperature increases produced by m-CPP given 24 h after the last dose of ritanserin, but did not cause a similar desensitization of DOI-induced hyperthermia. On the other hand, daily administration of both low (1.0 mg/kg per day) and high (5.0 mg/kg per day) doses of mianserin for 14 days caused desensitization of DOI-induced hyperthermia but did not cause desensitization of m-CPP-induced hyperthermia when these agonists were administered 48 h after the last dose of mianserin. These findings demonstrate functional subsensitivity of both 5-HT2A and 5-HT2C receptors mediating hyperthermia following both acute and chronic administration of 5-HT2A/5-HT2C receptor antagonists; some differences in time course and in responses to individual antagonists at 5-HT2A versus 5-HT2C sites were also observed.

Key words Metergoline Mesulergine Mianserin Ritanserin m-Chlorophenylpiperazine (±)1-(2 5-Dimethoxy-4-iodophenyl)-2-aminopropane 

Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • P. Mazzola-Pomietto
    • 1
  • Charanjit S. Aulakh
    • 1
  • Teresa Tolliver
    • 1
  • Dennis L. Murphy
    • 1
  1. 1.Laboratory of Clinical Science, National Institute of Mental Health, Building 10, Room 3D41, 10 Center Drive MSC 1264, Bethesda, MD 20892, USAUS