Alterations of In‐vitro 5‐HT Receptor Pharmacology as a Function of Multiple Treatment with 5‐Hydroxytryptamine or 8‐Hydroxy‐2‐(di‐N‐propylamino) Tetralin in Rat Isolated Aorta, Uterus and Fundus, and Guinea‐pig Isolated Trachea

Abstract— The effects of single and multiple (5, 10, or 15 days) administration of the 5‐HT1A agonist 8‐hydroxy‐2‐(di‐N‐propylamino) tetralin (8‐OH‐DPAT) (3 mg kg−1, i.p.) or 5‐HT (3 mg kg−1, i.p.) in‐vivo on the response of selected isolated smooth muscles to 5‐HT in‐vitro were investigated. Single dosing with 8‐OH‐DPAT did not alter the responses of the isolated tissues (rat aorta, uterus or fundus, or guinea‐pig trachea) to 5‐HT, while multiple dosing with 8‐OH‐DPAT produced rightward shifts and a suppression of the maximum response of all these tissues to 5‐HT, with the exception of the rat stomach fundus. Multiple administration of 5‐HT had no effect on the in‐vitro response of the tissues to 5‐HT. These data indicate that multiple administration of 8‐OH‐DPAT desensitizes or down‐regulates the peripheral 5‐HT2 receptors found on the rat aorta and uterus, and guinea‐pig trachea.