Effects of repeated doses of azapirones on rat brain 5-HT1A receptors and 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 each drug. The ED50 for buspirone was increased from 0.1 mg/kg to 1.8 mg/kg, and the ED50 for ipsapirone was increased from 0.7 mg/kg to 1.2 mg/kg. The binding properties (Kd and Bmax) of [3H]8-OH-DPAT to membranes of cerebral cortex and hippocampus were unaffected by chronic administration of either buspirone or ipsapirone. Chronic buspirone or ipsapirone administration increased the tolerance of the hypothalamic-pituitary-adrenal axis (HPAA) following a challenge by each drug. The ED50 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 activity of the HPAA by 63%. Chronic buspirone administration did not alter 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 erythrocyte plasma membrane were unaffected by either chronic or acute buspirone treatment, or by the addition of the drug to the in vitro assay systems.
Matheson
G K
GK
Department of Anatomy, Indiana University School of Medicine, Evansville 47712, USA. matheson@indyvax.iupui.edu
Raess
B U
BU
Tunnicliff
G
G
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002065:Buspirone / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003345:Corticosterone / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011743:Pyrimidines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D011743:Pyrimidines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002118:Calcium; D002065:Buspirone; D003345:Corticosterone