Stimulation of postsynaptic 5-HT1A receptors is responsible for the anticonflict effect of ipsapirone in rats.
Ipsapirone (1.25-10 mg kg-1), a non-benzodiazepine anxiolytic drug with high affinity for 5-hydroxytryptamine1A (5-HT1A) receptors, increased dose-dependently the number of punished licks in the drinking conflict test (Vogel test) in rats. The anticonflict effect of the drug administered at a dose of 5 mg kg-1 was not modified in animals with lesions of 5-HT neurones, produced by p-chloroamphetamine (PCA, 2 x 10 mg kg-1). The anticonflict effect of ipsapirone in PCA-pretreated rats was antagonized by the 5-HT1A receptor and alpha 1-adrenoceptor antagonist NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phthalimmido)]butylpiperazine hydrobromide; 0.5-1 mg kg-1), but not by the selective alpha 1-adrenoceptor blocker prazosin (0.5 mg kg-1). Neither NAN-190 nor prazosin affected the punished response in PCA-pretreated rats. The present results indicate that the anticonflict effect of ipsapirone depends on stimulation of postsynaptic 5-HT1A receptors.
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
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Przegalinski
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Chojnacka-Wojcik
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Filip
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D003220:Conflict, Psychological; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D010133:p-Chloroamphetamine / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D010879:Piperazines; D011743:Pyrimidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D010133:p-Chloroamphetamine; C043077:ipsapirone