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Induction of yawning by low doses of apomorphine (0.1, 0.2 and 0.4 mg) in healthy volunteers

Published online by Cambridge University Press:  28 April 2020

O. Blin
Clinique des Maladies Neuromusculaires, CHU Timone, 13005, Marseille
P. Danjou*
Département de Pharmacologie Clinique, Hôpital de la Pitié-Salpêtrière, 47 Bd de l‘Hôpital, 75651Paris Cedex 13
D. Warot
Département de Pharmacologie Clinique, Hôpital de la Pitié-Salpêtrière, 47 Bd de l‘Hôpital, 75651Paris Cedex 13
J. Fondarai
Service de Statistique, ERACM, 232 Bd Ste-Marguerite, 13009Marseille, France
A.J. Puech
Département de Pharmacologie Clinique, Hôpital de la Pitié-Salpêtrière, 47 Bd de l‘Hôpital, 75651Paris Cedex 13
*Correspondance and reprints
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The dopaminergic agonist apomorphine hydrochloride (0.1, 0.2 and 0.4 mg s.c.) compared to placebo in a double-blind, latin square design induced yawing in population of 8 healthy volunteers. Yawning was the only behavioral effect observed and was not dose-related, as all the 3 doses were equipotent. Yawning was maximum between 10 and 20 min post-injection and did not last longer than 20 min. Compared to the data in the literature, 0.1 mg is the lowest dose described as inducing yawning in man. Further studies using doses lower than 0.1 mg would be required to determine the highest inactive dose in order to use apomorphine-induced yawning as an index of CNS dopaminergic receptor sensitivity.



L'apomorphine, agoniste dopaminergique, administrée en sous-cutané à la dose de 0.1, 0.2 et 0.4 mg s.c., a entra— Baillements induits chez le volontaire sain par de faibles doses d’apomorphinené des baillements chez 8 volontaires sains, comparativement au placebo. Les baillements ont été les seuls effets comportementaux observés. Il n’existe pas de relation dose-effet aux trois doses étudiees mais les trois traitements sont differents du placebo entre la 10e et la 20e minute aprés l’injection. Des doses plus faibles seraient donc à étudier de maniére à se situer dans la zone de linéarité de la relation dose-effet, pour l’évaluation ultérieure de la sensibilité des systémes dopaminergiques centraux.

Original article
Copyright © European Psychiatric Association 1988

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Anias, J.Holmgren, B.Urba-Holmgren, R. & Eguibar, J.R. (1984) Circadian variation of yawning behavior. Acta Neurobiol. Exp. (Warsaw) 44, 179186Google ScholarPubMed
Corsini, G.U.Piccardi, M.P.Bochetta, A.Bernardi, F. & Del, Zompo M. (1981) Behavioural effects of apomorphine in man: Dopamine reccptor implications.In: Apomorphine and other Dopaminomimetics (Corsini, G.U. & Gessa, G.L., eds.), Raven Press, New YorkGoogle Scholar
Costentin, J.Dubuc, I. & Protais, P. (1983) Behavioural data suggesting the plurality of central dopamine receptors. CNS Receptors.In: Molecular Pharmacology to Behavior (Mandel, P. & Defreudis, H., eds.), Raven Press, New York, pp. 289297Google Scholar
Dourish, C.T.Cooper, S.J. & Philip, S.R. (1985a) Yawning elicited by systemic and intrastriatal injection of piribedil and apomorphine in the rat. Psychopharmacology 86, 175181CrossRefGoogle Scholar
Dourish, C.T. & Hutson, P.H. (1985b) Bilateral lesions of the striatum induced with 6-hydroxydopamine abolish apomorphine-induced yawning in rats. Neuropharmacology 24, 10511055CrossRefGoogle Scholar
Dubuc, I., Protais, P., Colboc, O. & Costentin, J. (1982) Antagonism of the apomorphine induced yawning by “ atypical” neuroleptics. Neuropharmacology 21, 12031206CrossRefGoogle ScholarPubMed
Ernst, A.M. (1967) Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats. Psychopharmacology 10, 316323CrossRefGoogle ScholarPubMed
Gower, A.J.Berendsen, H.H.G.Princen, M.M. & Broekkamp, C.L. (1984) The yawning penile erection syndrome as a model for putative dopamine autoreceptor activity. Eur. J. Pharmacol. 103, 8189CrossRefGoogle ScholarPubMed
Heusner, A.P. (1946) Yawning and associated phenomena. Physiol. Rev. 26, 156168CrossRefGoogle ScholarPubMed
Hindmarch, I. & Gudgeon, A.C. (1980) The effects of clobazam and lorazepam on aspects of psychomotor performances and car handling ability. Br. J. Clin. Pharmacol. 10, 145150CrossRefGoogle ScholarPubMed
Holmgren, B.Urba-Holmgren, R.Trucios, N.Zermeno, M. & Eguibar, J.R. (1985) Association of spontaneous and dopaminergic induced yawning and penile erections in the rats. Pharmacol. Biochem. Behav. 22, 3135CrossRefGoogle Scholar
Lal, S.Nair, N.P.V.Iskandar, H.I.Etienne, P.Wood, P.L.Schwartz, G. & Guyda, H. (1982) Effect of domperidone on apomorphine-induced growth hormone secretion in normal men. J. Neural Transm. 54, 7584CrossRefGoogle ScholarPubMed
Lal, S.Grassino, A.Thavundayil, J.X. & Dubrovsky, B. (1987) A simple method for the study of yawning in man induced by the dopamine agonist apomorphine. Prog. Neuropsychopharmacol. & Biol. Psychiatry 11, 223228CrossRefGoogle Scholar
Mogilnicka, E. & Klimek, V. (1977) Drugs affecting dopamine neurons and yawning behavior. Pharmacol. Biochem. Behav. 7, 303—305CrossRefGoogle ScholarPubMed
Mogilnicka, E.Boissard, C.G. & Delini-Stula, A. (1984) Effects of apomorphine, TL 99 and 3-PPP on yawning in rats. Neuropharmacology 23, 1922CrossRefGoogle ScholarPubMed
Morelli, M.Longoni, R.Spina, L. & Di, Chiara G. (1986) Antagonism of apomorphine induced yawning by SCH 23390: evidence against the autoreceptor hypothesis. Psychopharmacology 89, 259260CrossRefGoogle ScholarPubMed
Nair, N.P.V.Lal, S.Thavundayil, J.W.Wood, P.L.Etienne, P. & Guyda, H. (1984) CCK-33 antagonizes apomorphine-induced growth hormone secretion and increases basal prolaetin levels in man. Neuropeptides 4, 281291CrossRefGoogle ScholarPubMed
Nickolson, V.J. & Berendsen, H.H.G. (1980) Effects of the potential neuroleptic peptide DES-tyrosine-gamma endorphin and haloperidol on apomorphine-induced behavioural syndromes in rats and mice. Life Sci. 27, 13771385CrossRefGoogle ScholarPubMed
Okuyama, S.Shimamura, H.Hashimoto, S. & Aihara, H. (1986) Electrophysiological and behavioral assessments of dopamine autoreceptor activation to apomorphine in rats. Arch. Int. Pharmacodyn. Ther. 284, 246254Google ScholarPubMed
Puech, A.J.Simon, P.Chermat, R. & Boissier, Y. (1974) Profil neuropsychologique de l’apomorphine. J. Pharmacol. 5, 241254Google Scholar
Serra, G.Collu, M. & Gessa, G.L. (1987) Yawning is elicited by D2 dopamine agonists but is blocked by the DI antagonist, SCH 23390. Psychopharmacology 91, 330333CrossRefGoogle Scholar
Stahle, L. & Ungerstedt, U. (1984) Assessment of dopamine autoreceptor properties of apomorphine and ( +)-3-PPP and (-)-3-PPP by recording yawning behavior in rats. Eur. J. Pharmacol. 98, 307310CrossRefGoogle ScholarPubMed
Szechtman, H. (1984) Timing of yawns induced by small doses of apomorphine and its alteration by naloxone. Prog. NeuropsychopharmacoL Biol. & Psychiatry 8, 743746CrossRefGoogle Scholar
Ushijima, I.Mizuki, Y.Yamada, M.Noda, Y.Yamada, K. & Furukawa, T. (1985) Characteristics of yawning behavior induced by apomorphine, physostigmine and pilocarpine. Arch. Int. Pharmacodyn. Ther. 273, 196201Google ScholarPubMed
Yamada, K. & Furukawa, T. (1980) Direct evidence for involvement of dopaminergic inhibition and cholinergic activation in yawning. Psychopharmacology 67, 3943CrossRefGoogle ScholarPubMed
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