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

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-DP AT) (3 mg kg(-1), i.p.) or 5-HT (3 mg kg(-1), i.p.) in-vivo on the res ponse of selected isolated smooth muscles to 5-HT in-vitro were invest igated. Single dosing with 8-OH-DPAT did not alter the responses of th e isolated tissues (rat aorta, uterus or fundus, or guinea-pig trachea ) to 5-HT, while multiple dosing with 8-OH-DPAT produced rightward shi fts and a suppression of the maximum response of all these tissues to 5-HT, with the exception of the rat stomach fundus. Multiple administr ation 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 d esensitizes or down-regulates the peripheral 5-HT2 receptors found on the rat aorta and uterus, and guinea-pig trachea.