Modification of the discriminative stimulus effects of 8-OH-DPAT, buspirone and the beta-adrenoreceptor antagonist pindolol after chronic administration of the 5-HT(1A) agonist 8-OH-DPAT in the pigeon.
The involvement of adrenoreceptor blocking drugs with the 5-HT(1A)-mediated discriminative stimulus was studied in pigeons trained to discriminate the 5-HT(1A) receptor agonist 8-OH-DPAT (0.3mg/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-HT(1A) agonist buspirone, before, during and after (8-OH-DPAT and pindolol) chronic administration of 8-OH-DPAT (3.0mg/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-HT(1A) 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-HT(1A) 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-HT(1A) agonists and beta-adrenoceptor blocking drugs that only become apparent after 2 to 4 weeks of chronic administration.
Department of Psychiatry, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 20814-4799, USA.
L.
L
Zhang
J.E.
JE
Barrett