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

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.

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  1. Laboratory of Clinical Science, National Institute of Mental Health, Building 10, Room 3D41, 10 Center Drive MSC 1264, Bethesda, MD 20892, USA, , , , , , US

    P. Mazzola-Pomietto, Charanjit S. Aulakh, Teresa Tolliver & Dennis L. Murphy

Authors
  1. P. Mazzola-Pomietto
  2. Charanjit S. Aulakh
  3. Teresa Tolliver
  4. Dennis L. Murphy
Additional information

Received: 14 June 1996 / Final version: 28 August 1996

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Mazzola-Pomietto, P., Aulakh, C., Tolliver, T. et al. Functional subsensitivity of 5-HT2A and 5-HT2C receptors mediating hyperthermia following acute and chronic treatment with 5-HT2A/2C receptor antagonists. Psychopharmacology 130, 144–151 (1997). https://doi.org/10.1007/s002130050222

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