Functional subsensitivity of 5-HT2A and 5-HT2C receptors mediating hyperthermia following acute and chronic treatment with 5-HT2A/2C receptor antagonists.
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.
Mazzola-Pomietto
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P
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892, USA.
Aulakh
C S
CS
Tolliver
T
T
Murphy
D L
DL
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D005334:Fever / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013997:Time Factors
D000662:Amphetamines; D010879:Piperazines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; C015068:1-(3-chlorophenyl)piperazine