DISCRIMINATIVE STIMULUS CHARACTERISTICS OF BMY-14802 IN THE PIGEON

Pigeons were trained to discriminate intramuscular injections of 5.6 m g/kg BMY 14802, a drug that has relatively high affinity for sigma bin ding sites, from saline in a two-key operant procedure, Many compounds that displace sigma binding failed to produce BMY 14802-like discrimi native stimulus effects; these included (+)-SKF 10,047, (+)3-PPP, DTG and MR 2035; the typical antipsychotic haloperidol; the putative antip sychotics tiospirone, cinuperone and rimcazole; and the uncompetitive NMDA antagonist phencyclidine. In addition, MR 2035 and tiosperone fai led to antagonize the discriminative stimulus effects of BMY 14802. Th e selective D-2 antagonist eticlopride and the norepinephrine uptake b locker and antidepressant desmethylimipramine also failed to evoke sub stantial BMY 14802-appropriate responding. In contrast to sigma ligand s and other reference compounds, the 5-HT1A agonists buspirone, 8-OH-D PAT and spiroxatrine dose-dependently produced BMY 14802-like discrimi native stimulus effects. The limited-efficacy 5-hydroxytryptamine (HT) (1A) agonist NAN 190 did not produce BMY 14802-like discriminative eff ects; 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 p roduce substantial BMY 14802-appropriate responding; such as 5-HT1 ago nist l-5-HTP; 5-HT1A/B agonist RU245695; 5-HT1B/1C agonist m-CPP; 5-HT 1C/2 agonist quipazine; 5-HT1C/2 antagonists, metergoline and the atyp ical antipsychotic clozapine; and 5-HT3 antagonist ondansetron. Also, metergoline, ondansetron and pirenpirone failed to antagonize the stim ulus effects of BMY 14802. These results indicate that the discriminat ive stimulus effects of BMY 14802 are serotonergically mediated primar ily by 5-HT1A receptors rather than by sigma sites.