5-HT1A and 5-HT1B agonists play a differential role on the respiratory frequency in rats.
The effect of the putative 5-HT1A agonists 8-OH-DPAT and ipsapirone and 5-HT1B agonists TFMPP and m-CPP on respiratory activity in rats has been examined. In chloral hydrate-anesthetized rats, respiratory counts were decreased in a dose-dependent manner by both TFMPP and m-CPP, with an ED50 of 0.30 mg/kg (1.1 mumol/kg) and 3.0 mg/kg (11.0 mumol/kg) respectively. In contrast, both 5-HT1A agonists tested, 8-OH-DPAT and ipsapirone, produced an increase in respiratory rate at all doses tested. Moreover, the TFMPP-induced decrease in respiratory rate was antagonized by 8-OH-DPAT. The 5-HT2 antagonist ketanserin had no effect on the TFMPP-induced decrease in respiratory activity. However, methylsergide (5-HT1/5-HT2 antagonist) and (-)-cyanopindolol (5-HT1B antagonist) antagonized the TFMPP-induced respiratory rate decrease. The results of these experiments, coupled with the predominant presence of 5-HT1B receptors in the lower brainstem, pons, and medulla, as established by autoradiography studies, suggest a possible involvement of the 5-HT1B receptor subtype in the control of respiratory mechanisms, especially those involved in respiratory rhythmicity.
Edwards
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Department of Psychiatry and Behavioral Science, State University of New York at Stony Brook 11794-8191.
Whitaker-Azmitia
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PM
Harkins
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K
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D012119:Respiration / Q000187:drug effects*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D009281:Naphthalenes; D010879:Piperazines; D011743:Pyrimidines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C018406:1-(3-trifluoromethylphenyl)piperazine; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C015068:1-(3-chlorophenyl)piperazine