ATTENUATION OF HORMONE RESPONSES TO THE 5-HT1A AGONIST IPSAPIRONE BY LONG-TERM TREATMENT WITH FLUOXETINE, BUT NOT DESIPRAMINE, IN MALE-RATS

The present study had two objectives: (1) to provide information on ne uroendocrine challenge tests that can lead to diagnostic tests in huma ns; and (2) to confirm our previous observation that chronic fluoxetin e selectively inhibits serotonin (5-HT1A) receptor function. We determ ined the effect of chronic fluoxetine and desipramine (DMI) on the hor mone response to ipsapirone, a 5-HT1A agonist and a potential anxiolyt ic drug. Ipsapirone increased oxytocin, adrenocorticotropic hormone (A CTH), corticosterone, and prolactin, but nor renin or vasopressin conc entrations in plasma. Chronic fluoxetine, but not DMI, significantly i nhibited the effect of ipsapirone on plasma oxytocin, ACTH and cortico sterone concentrations. Chronic fluoxetine also reduced the B-max for H-3-8-hydroxy-2-(dipropylamino) tetralin (H-3-8-OH-DPAT) labelled 5-HT 1A receptors in the midbrain. Neither antidepressant altered the densi ty or affinity of 5-HT uptake sites. In conclusion, the present result s confirm our previous results using 8-OH-DPAT as a challenge, and sug gest that chronic 5-HT uptake inhibition results in adaptive changes l eading to decreased function of the 5-HT1A receptor system. Finally, b ecause ipsapirone may be administered to humans, it might be usable to evaluate 5-HT1A receptor function in depressed patients.