Vol. 284, Issue 1, 1-9, 1998

Discriminative Stimulus Characteristics of BMY 14802 in the Pigeon¹

Susan A. Vanecek² , William D. Essman³ , Duncan P. Taylor⁴ and James H. Woods

Departments of Pharmacology (S.A.V., J.H.W.) and Psychology (W.D.E., J.H.W.), The University of Michigan Medical School, Ann Arbor, MI; and CNS Neuropharmacology (D.P.T.), Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT

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-HT_1A 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 l-5-HTP; 5-HT_1A/1B agonist RU24969; 5-HT_1B/1C agonist m-CPP; 5-HT_1C/2 agonist quipazine; 5-HT_1C/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-HT_1A receptors rather than by sigma sites.