The role of postsynaptic 5-HT1A receptors in the anticonflict effect of ipsapirone.
In the present paper we have studied the anticonflict effect (in the Vogel test) of ipsapirone, a partial agonist of 5-hydroxytryptamine1A (5-HT1A) receptors, administered to the hippocampus of rats. In addition, a comparison of the effect of ipsapirone with the effect of other 5-HT1A receptor ligands (busipone, gepirone and 8-OH-DPAT) has been carried out. Finally, the interaction between ipsapirone and NAN-190 (an antagonist of 5-HT1A receptors and alpha 1-adrenoceptors) has also been examined. It has been found that ipsapirone injected intrahippocampally (i.hp.) in doses of 0.3, 1 and 3 micrograms (bilaterally) shows an anticonflict effect by increasing the number of punished licks by about 36, 151 and 109%, respectively. A similar effect has also been found after i.hp. injections of buspirone (0.3-3 micrograms), gepirone (3-30 micrograms) and 8-OH-DPAT (0.3-3 micrograms). We have also demonstrated that the anticonflict effect of ipsapirone injected i.hp. is antagonized by NAN-190 administered i.hp. (0.3 or 1 microgram) or intraperitoneally (i.p., 1 mg/kg). Furthermore, NAN-190 injected i.hp. (0.3 microgram) antagonizes the anticonflict effect of ipsapirone administered i.p. (5 mg/kg). At the same time, the anticonflict effects of ipsapirone are not affected by prazosin (0.3-1 microgram i.hp. or 0.5-1 mg/kg i.p.), a selective antagonist of alpha 1-adrenoceptors. Our results seem to indicate that the anticonflict effect of ipsapirone stems from stimulation of postsynaptic 5-HT1A receptors in the hippocampus.
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
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Przegaliński
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Tatarczyńska
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Kłodzińska
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Chojnacka-Wójcik
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003220:Conflict, Psychological; D004327:Drinking Behavior / Q000187:drug effects; D004597:Electroshock; D006624:Hippocampus / Q000033:anatomy & histology; D007267:Injections; D008297:Male; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D012054:Reinforcement, Psychology; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*
D010879:Piperazines; D011743:Pyrimidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; C043077:ipsapirone; D011224:Prazosin