Spiroxatrine as a discriminative stimulus: Effects depend on pharmacological history

Abstract Spiroxatrine, a compound with effects on both dopamine (DA) and serotonin (5‐HT) neurotransmitter systems, was established as a discriminative stimulus in pigeons. Along with novel anxiolytic nonbenzodiazepine compounds such as buspirone and ipsapirone, spiroxatrine has been suggested to interact at the 5‐HT 1A receptor subtype. Following the administration of 0.3 mg/kg spiroxatrine, every 30th consecutive peck on one key produced food, whereas following saline administration, pecks on the alternate key produced food. After dose‐response curves with spiroxatrine were obtained, two pigeons were tested first with buspirone, which, like spiroxatrine, also has effects on both 5‐HT 1A and DA systems, and two pigeons were tested first with the more specific 5‐HT 1A compounds 2‐mPP (1‐[2‐methoxyphenyl]piperazine) or 8‐OH‐DPAT (8‐hydroxy‐2‐[di‐n‐propylamino]tetralin). All pigeons responded on the drug‐appropriate key when these compounds were the initial drugs substituted for spiroxatrine. Pigeons tested first with 2‐mPP or 8‐OH‐DPAT also responded on the drug‐appropriate key when buspirone was administered in subsequent tests. However, when first tested with buspirone then tested subsequently with 8‐OH‐DPAT, pigeons responded on the saline key at all 8‐OH‐DPAT doses and did so throughout the study whenever any selective 5‐HT 1A ligand was substituted. Drug history may enhance or diminish specific stimulus effects of drugs with multiple stimulus dimensions. Drugs with multiple stimulus effects may permit the specific study of behavioral and pharmacological variables that affect the discriminative stimulus effects of drugs and, perhaps, also their behavioral effects under other circumstances.