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Discriminative stimulus characteristics of BMY 14802 in the pigeon.
J Pharmacol Exp Ther. 1998 Jan; 284(1):1-9.JP

Abstract

Pigeons were trained to discriminate intramuscular injections of 5.6 mg/kg BMY 14802, a drug that has relatively high affinity for sigma binding sites, from saline in a two-key operant procedure. Many compounds that displace sigma binding failed to produce BMY 14802-like discriminative stimulus effects; these included (+)-SKF 10,047, (+)3-PPP, DTG and MR 2035; the typical antipsychotic haloperidol; the putative antipsychotics tiospirone, cinuperone and rimcazole; and the uncompetitive NMDA antagonist phencyclidine. In addition, MR 2035 and tiosperone failed to antagonize the discriminative stimulus effects of BMY 14802. The selective D2 antagonist eticlopride and the norepinephrine uptake blocker and antidepressant desmethylimipramine also failed to evoke substantial BMY 14802-appropriate responding. In contrast to sigma ligands and other reference compounds, the 5-HT1A agonists buspirone, 8-OH-DPAT and spiroxatrine dose-dependently produced BMY 14802-like discriminative stimulus effects. The limited-efficacy 5-hydroxytryptamine (HT)1A agonist NAN 190 did not produce BMY 14802-like discriminative effects; however, it did competitively antagonize the stimulus effects of BMY 14802 and the BMY 14802-like stimulus effects of (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin. Other serotonergic compounds failed to produce substantial BMY 14802-appropriate responding; such as 5-HT1 agonist I-5-HTP; 5-HT1A/1B agonist RU24969; 5-HT1B/1C agonist m-CPP; 5-HT1C/2 agonist quipazine; 5-HT1C/2 antagonists, metergoline and the atypical antipsychotic clozapine; and 5-HT3 antagonist ondansetron. Also, metergoline, ondansetron and pirenpirone failed to antagonize the stimulus effects of BMY 14802. These results indicate that the discriminative stimulus effects of BMY 14802 are serotonergically mediated primarily by 5-HT1A receptors rather than by sigma sites.

Authors+Show Affiliations

Department of Pharmacology, University of Michigan Medical School, Ann Arbor, USA. svanecek@etowaha.uhsc.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9435153

Citation

Vanecek, S A., et al. "Discriminative Stimulus Characteristics of BMY 14802 in the Pigeon." The Journal of Pharmacology and Experimental Therapeutics, vol. 284, no. 1, 1998, pp. 1-9.
Vanecek SA, Essman WD, Taylor DP, et al. Discriminative stimulus characteristics of BMY 14802 in the pigeon. J Pharmacol Exp Ther. 1998;284(1):1-9.
Vanecek, S. A., Essman, W. D., Taylor, D. P., & Woods, J. H. (1998). Discriminative stimulus characteristics of BMY 14802 in the pigeon. The Journal of Pharmacology and Experimental Therapeutics, 284(1), 1-9.
Vanecek SA, et al. Discriminative Stimulus Characteristics of BMY 14802 in the Pigeon. J Pharmacol Exp Ther. 1998;284(1):1-9. PubMed PMID: 9435153.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Discriminative stimulus characteristics of BMY 14802 in the pigeon. AU - Vanecek,S A, AU - Essman,W D, AU - Taylor,D P, AU - Woods,J H, PY - 1998/1/22/pubmed PY - 1998/1/22/medline PY - 1998/1/22/entrez SP - 1 EP - 9 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 284 IS - 1 N2 - Pigeons were trained to discriminate intramuscular injections of 5.6 mg/kg BMY 14802, a drug that has relatively high affinity for sigma binding sites, from saline in a two-key operant procedure. Many compounds that displace sigma binding failed to produce BMY 14802-like discriminative stimulus effects; these included (+)-SKF 10,047, (+)3-PPP, DTG and MR 2035; the typical antipsychotic haloperidol; the putative antipsychotics tiospirone, cinuperone and rimcazole; and the uncompetitive NMDA antagonist phencyclidine. In addition, MR 2035 and tiosperone failed to antagonize the discriminative stimulus effects of BMY 14802. The selective D2 antagonist eticlopride and the norepinephrine uptake blocker and antidepressant desmethylimipramine also failed to evoke substantial BMY 14802-appropriate responding. In contrast to sigma ligands and other reference compounds, the 5-HT1A agonists buspirone, 8-OH-DPAT and spiroxatrine dose-dependently produced BMY 14802-like discriminative stimulus effects. The limited-efficacy 5-hydroxytryptamine (HT)1A agonist NAN 190 did not produce BMY 14802-like discriminative effects; however, it did competitively antagonize the stimulus effects of BMY 14802 and the BMY 14802-like stimulus effects of (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin. Other serotonergic compounds failed to produce substantial BMY 14802-appropriate responding; such as 5-HT1 agonist I-5-HTP; 5-HT1A/1B agonist RU24969; 5-HT1B/1C agonist m-CPP; 5-HT1C/2 agonist quipazine; 5-HT1C/2 antagonists, metergoline and the atypical antipsychotic clozapine; and 5-HT3 antagonist ondansetron. Also, metergoline, ondansetron and pirenpirone failed to antagonize the stimulus effects of BMY 14802. These results indicate that the discriminative stimulus effects of BMY 14802 are serotonergically mediated primarily by 5-HT1A receptors rather than by sigma sites. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/9435153/Discriminative_stimulus_characteristics_of_BMY_14802_in_the_pigeon_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9435153 DB - PRIME DP - Unbound Medicine ER -