EFFECTS OF REPEATED DOSES OF AZAPIRONES ON RAT-BRAIN 5-HT1A RECEPTORSAND PLASMA-CORTICOSTERONE LEVELS

Chronic buspirone or ipsapirone (3 mg/kg, twice daily) administration to rats for 10 days decreased the sensitivity of inhibition of single unit activity of serotonergic dorsal raphe neurons to a challenge by e ach drug. The ED(50) for buspirone was increased from 0.1 mg/kg to 1.8 mg/kg, and the ED(50) for ipsapirone was increased from 0.7 mg/kg to 1.2 mg/kg. The binding properties (K-d and B-max) of [H-3]8-OH-DPAT to membranes of cerebral cortex and hippocampus were unaffected by chron ic administration of either buspirone or ipsapirone. Chronic buspirone or ipsapirone administration increased the tolerance of the hypothala mic-pituitary-adrenal axis (HPAA) following a challenge by each drug. The ED(50) for elevation of plasma corticosterone levels was increased from 4.0 mg/kg to 7.6 mg/kg for buspirone and 6.2 mg/kg to 8.0 mg/kg for ipsapirone. Chronic buspirone administration decreased the basal a ctivity of the HPAA by 63%, Chronic buspirone administration did not a lter the plasma corticosterone response of the HPAA to a 1-min episode of rotational stress. (Mg2+)-ATPase, (Na+ + K+)-ATPase, (Ca2+ + Mg2+) -ATPase and calmodulin-stimulated (Ca2+ + Mg2+)-ATPase activities of e rythrocyte plasma membrane were unaffected by either chronic or acute buspirone treatment, or by the addition of the drug to the in vitro as say systems.