Antagonism of 8-OH-DPAT-induced behaviour in rats.

Selective activation of the 5-HT1A receptor induces lower lip retraction (LLR) in rats. 8-Hydroxy-dipropylamino tetralin (8-OH-DPAT)-induced LLR could not be antagonised by the 5-HT antagonists methysergide, metergoline or mesulergine. In fact, some 5-HT antagonists induced LLR. However, 8-OH-DPAT-induced LLR could be antagonised by pindolol, spiperone, spiroxatrine and NAN-190, but not ...
by the beta 1-adrenoceptor antagonist metoprolol, the beta 2-adrenoceptor antagonist butoxamine or the dopamine antagonist haloperidol. This antagonism was competitive as the dose-response curve of 8-OH-DPAT was shifted to the right. Pindolol, spiperone, spiroxatrine and NAN-190 all have a high affinity for the 5-HT1A receptor. This indicates that blockade of 8-OH-DPAT-induced LLR is only possible by selective blockade of 5-HT1A receptors. A possible mechanism of action is discussed. The increased defecation induced by 8-OH-DPAT could be antagonised by pindolol and NAN-190. The effect of spiroxatrine and haloperidol on the 8-OH-DPAT-induced increase in defecation was bimodal: an increase after a low and a decrease after a high dose of 8-OH-DPAT. Metoprolol and butoxamine had no effect on the 8-OH-DPAT-induced increase in defecation, thereby excluding an influence of beta-adrenoceptors.
Mesh Terms:
8-Hydroxy-2-(di-n-propylamino)tetralin, Animals, Behavior, Animal, Defecation, Dose-Response Relationship, Drug, Lip, Male, Rats, Rats, Inbred Strains, Receptors, Serotonin, Serotonin Antagonists, Tetrahydronaphthalenes
Eur. J. Pharmacol.
Date: Oct. 02, 1990
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