Selective activation of 5HT1A receptors induces lower lip retraction in the rat.

The induction of lower lip retraction (LLR) by serotonergic (5HT) compounds and antagonism of LLR by compounds acting via a variety of receptor systems was investigated. LLR could be induced by subcutaneous injection of 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), buspirone, ipsapirone or RU 24969. Inactive were the putative 5HT1B,1C agonist 1-(3'chlorophenyl)-piperazine (mCCP), the 5HT2,1C agonist (dl)-1-(2,5 dimethoxy-4-iodophenyl)-2-aminopropane (DOI), the 5HT reuptake inhibitors citalopram and paroxetine and the 5HT-releasing compounds parachloroamphetamine (PCA) and fenfluramine. 5-Methoxy-N,N-dimethyltryptamine (5-MeODMT) induced lower lip retraction after pretreatment with metergoline, cyproheptadine or ritanserin but not by itself. 8-OH-DPAT-induced LLR could be antagonised by the direct and indirect 5HT agonists mCPP, DOI, 5-MeODMT, PCA, fenfluramine and high doses of paroxetine, but not by the 5HT antagonists metergoline, methysergide, mesulergine, GR38032F, xylamidine or pirenperone. The dopamine agonists apomorphine and pergolide antagonised 8-OH-DPAT-induced LLR, whereas SKF 38393 was weakly active. No significant antagonism was found with the dopamine antagonists haloperidol and spiperone, the alpha 2 agonist clonidine and the alpha 1 antagonist prazosin and the alpha 2 antagonist idazoxan. Also inactive were the antihistaminic mepyramine, the anticholinergic atropine, the opiate antagonist naloxone and the anxiolytic chlordiazepoxide. The results suggest that, in vivo, functional interactions take place between the various 5HT receptors. The hypothesis that lower lip retraction is induced by compounds directly and selectively stimulating 5HT1A receptors is discussed.