Evidence for the involvement of 5-HT1A receptors in the anticonflict effect of ipsapirone in rats.
The anticonflict activity of ipsapirone, a non-benzodiazepine anxiolytic drug, with high affinity for 5-hydroxytryptamine1A (5-HT1A) receptors, was studied in the drinking conflict test in the rat. The drug, administered in doses 1.25-20 mg/kg increased the number of punished licks, with the maximum effect observed after doses of 5-20 mg/kg of ipsapirone. The anticonflict effect of ipsapirone (5 mg/kg) was dose-dependently antagonized by the 5-HT1A receptor, alpha 1-adrenoceptor and dopamine receptor antagonist, NAN-190 (0.25-1 mg/kg) and by the beta-adrenoceptor blocker, SDZ 21009, which also has a high affinity for 5-HT1A and 5-HT1B receptors (2-8 mg/kg). On the other hand, the non-selective 5-HT receptor antagonist, metergoline (2 and 4 mg/kg), the 5-HT2/5-HT1C receptor antagonist, ritanserin (0.25 and 0.5 mg/kg), the selective alpha 1-adrenoceptor blocker, prazosin (0.25-0.5 mg/kg) and the beta-blockers, betaxolol (8 mg/kg) and ICI 118 551 (8 mg/kg), which have no affinity for 5-HT receptors, did not affect the anticonflict action of ipsapirone. The effect of ipsapirone was also not modified in animals with lesions of 5-HT neurones, produced by p-chloroamphetamine (PCA--2 x 10 mg/kg). These results suggest that the anticonflict effect of ipsapirone in the Vogel test, results from its interaction with 5-HT1A receptors, which are probably located postsynaptically.
Institute of Pharmacology, Polish Academy of Sciences, Kraków.
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Chojnacka-Wójcik
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Przegaliński
D000818:Animals; D014151:Anti-Anxiety Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects; D004327:Drinking Behavior / Q000187:drug effects; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / 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; D008711:Metergoline; C043077:ipsapirone