MODIFICATION OF THE DISCRIMINATIVE STIMULUS EFFECTS OF 8-OH-DPAT, BUSPIRONE AND THE BETA-ADRENOCEPTOR ANTAGONIST PINDOLOL AFTER CHRONIC ADMINISTRATION OF THE 5-HT1A AGONIST 8-OH-DPAT IN THE PIGEON

The involvement of adrenoreceptor blocking drugs with the 5-HT1A-mediated discriminative stimulus was studied in pigeons trained to discriminate the 5-HT1A receptor agonist 8-OH-DPAT (0.3 mg/kg) from saline. Cumulative dose-response curves were determined for 8-OH-DPAT, the beta-adrenergic antagonist pindolol, the alpha-1-antagonist prazosin, as well as for the 5-HT1A agonist buspirone, before, during and after (8-OH-DPAT and pindolol) chronic administration of 8-OH-DPAT (3.0 mg/kg/day for 6 weeks). The dose-response curves for 8-OH-DPAT and buspirone, which substituted for 8-OH-DPAT, were shifted to the left during chronic 8-OH-DPAT administration. Prazosin did not substitute for 8-OH-DPAT at any time throughout the course of the study. Pindolol did not substitute for 8-OH-DPAT before chronic administration, but did so during and after 8-OH-DPAT was administered chronically. Chronic administration of 8-OH-DPAT resulted in a heightened sensitivity not only to the 5-HT1A agonists 8-OH-DPAT and buspirone, but also to what appear to be partial agonist effects of pindolol. This approach represents a first step in the in vivo characterization of changes in 5-HT1A sensitivity after chronic administration of 8-OH-DPAT using the drug discrimination procedure. This method may Provide a useful behavioral model with which to investigate the mechanisms of anxiolytic and antidepressant effects of 5-HT1A agonists and beta-adrenoceptor blocking drugs that only become apparent after 2 to 4 weeks of chronic administration.