The behavioural, but not the hypothermic or corticosterone, response to 8-hydroxy-2-(DI-n-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-HT2 receptors and alpha 1- and alpha 2-adrenoceptors (corticosterone response) seems to be excluded.
Przegaliński
E
E
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Ismaiel
A M
AM
Chojnacka-Wójcik
E
E
Budziszewska
B
B
Tatarczyńska
E
E
Błaszczyńska
E
E
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood*; D008297:Male; D009281:Naphthalenes / Q000037:antagonists & inhibitors*; D010869:Pindolol / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013134:Spiperone / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D009281:Naphthalenes; D010879:Piperazines; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D013134:Spiperone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D012110:Reserpine; D010869:Pindolol; D003345:Corticosterone