THE BEHAVIORAL, BUT NOT THE HYPOTHERMIC OR CORTICOSTERONE, RESPONSE TO 8-HYDROXY-2-(DI-NORMAL-PROPYLAMINO)-TETRALIN, IS ANTAGONIZED BY NAN-190 IN THE RAT

The 5-HT1A receptor antagonistic properties of 1-(2-methoxyphenyl)-4-[4-(2-phthalimmido) butyl] piperazine (NAN-190) were studied in rats: its effect on the 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT)-induced behavioural syndrome (flat body posture and reciprocal forepaw treading), hypothermia and secretion of corticosterone, i.e. responses mediated by 5-HT1A receptors, were examined. The drug NAN-190 (1-8 mg/kg) antagonized dose-dependently behavioural effects of 8-OH-DPAT (in both non-reserpinized and reserpine-pretreated animals); however, when administered in doses of 0.5-4 mg/kg, it did not affect the hypothermic or the hormonal response to 8-OH-DPAT. However, NAN-190 (1-8 mg/kg) given alone, produced hypothermia and increased the concentration of corticosterone in serum. The latter effects of NAN-190 were not reduced by (-)pindolol or spiperone. Moreover, the NAN-190-induced secretion of corticosterone was not affected by ketanserin, prazosin or yohimbine. The above results indicate that NAN-190 acts as a 5-HT1A receptor antagonist, only in the model of the 8-OH-DPAT-induced behavioural syndrome. The lack of effect of NAN-190 on the hypothermic or corticosterone response to 8-OH-DPAT most probably results from its own action which mimics the effects of 8-OH-DPAT. The mechanisms responsible for the NAN-190-induced hypothermia and secretion of corticosterone are still unknown, though stimulation of 5-HT1A receptors (either effect), 5-HT2receptors and α1- and α2-adrenoceptors (corticosterone response) seems to be excluded. © 1990.