TY - JOUR T1 - Pharmacological characterization of in vivo properties of putative mixed 5-HT1A agonist/5-HT2A/2C antagonist anxiolytics. I. Antipunishment effects in the pigeon. AU - Kleven,M S, AU - Koek,W, PY - 1996/2/1/pubmed PY - 1996/2/1/medline PY - 1996/2/1/entrez SP - 388 EP - 97 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 276 IS - 2 N2 - A conflict procedure in pigeons was used to characterize the antipunishment effects of the putative mixed 5-hydroxytryptamine (5-HT)1A agonist/5-HT2A/2C antagonists WY 50,324, CGS 18102A, LEK 8804 and FG 5974 and to further investigate interactions between the antipunishment effects of the 5-HT1A agonists buspirone and 8-OH-DPAT [8-hydroxy-2-(di-n-propylamino)tetralin] administered in combination with the mixed 5-HT2A/2C antagonist ritanserin and the alpha 1 antagonist prazosin. The 5-HT1A agonists, buspirone and 8-OH-DPAT, which lack affinity for 5-HT2A/2C receptors, produced dose-related increases in punished responding. Of the compounds with a mixed binding profile, only WY 50,324 showed effects that were comparable to those observed after 8-OH-DPAT, whereas FG 5974 and CGS 18102A exhibited limited effects on punished responding, and LEK 8804 was ineffective. Administration of a relatively low, behaviorally active dose of ritanserin (0.16 mg/kg) significantly enhanced the potency of 8-OH-DPAT and buspirone to increase punished responding from 8 to 50-fold without altering their effects on unpunished responding. Importantly, ritanserin failed to increase the number of doses of 8-OH-DPAT that significantly increased punished responding. In contrast, prazosin (2.5 mg/kg) significantly enhanced the potency and increased the number of doses of buspirone exerting significant effects on punished responding, but did not alter the effects of 8-OH-DPAT. Taken together, the results neither explain the suggested greater efficacy in producing anxiolytic effects of compounds with putative mixed 5-HT1A agonist and 5-HT2A/2C antagonist properties, nor confirm a proposed interaction between alpha1 adrenoreceptors and 5-HT1A agonists in preclinical tests of anxiolytic activity. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/8632301/Pharmacological_characterization_of_in_vivo_properties_of_putative_mixed_5_HT1A_agonist/5_HT2A/2C_antagonist_anxiolytics__I__Antipunishment_effects_in_the_pigeon_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8632301 DB - PRIME DP - Unbound Medicine ER -