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11 novembre 2002
Pharmacol Biochem Behav 1979; 11; 3; 371-2
Serotonergic modulation of yawning
Urba-Holmgren R, Holmgren B, Rodriguez R, Gonzalez RM
Centro nacional de investigaciones cientificas, La Habana, Cuba
Marini JL Serotonergic and dopaminergic effects on yawning in the cat
Tous les travaux de MR Melis & A Argiolas 
Tous les travaux de M Eguibar & G Holmgren


Yawning is a fixed innate motor pattern that has been rather neglected in experimental behavioral studies. Nevertheless, some attention bas recently been focussed on its tinderlying neurotransmitter mechanisms. From results of experiments mainly performed in infant rats, it bas been suggested that central cholinergic synapses may play an important role in relation to yawning, since cholinomimetic drugs (physostigmine and pilocarpine) greatly influence its frequency. The responsible receptors seem to be of the muscarinic type, because the yawning induicing effect of the two above mentioned drugs is blocked by scopolamine.

Other experiments performed in adult male albino rats indicate that some dopaminergic (DA) component might be present in yawning. Low doses of systemically injected DA agonists (apomorphine, piribedil, amphetamine, nomifensine and L-DOPA) produce recurrent episodes of yawning, responses which are completely inhibited by spiperone.

As yawning seems to be commonly associated with transitional phases in the sleep-waking cycle, particularly with the state of drowsiness preceding or following sleep, and strong evidence links the serotonergic pathways wilh slowwave sleep, it seemed worthwhile to explore the possible participation of serotonergic mechanisms in the induction or modulation of yawning.

Method : Most of the experiments to be reported were performed in infant (6-7 day-old) Wistar rats, born in the laboratory, their age being estimated with an approximation of +- 8 hours. All litters were reduced to eight pups 24 to 36 hr after birth. The animals were randornly distributed among experimental and control groups. Yawning was induced by intraperitoneal (IP) injection of physostigmine (BDH) in doses of 0,15 mgKg . The animals were placed in glass cylinders 18 cm in diameter, the floor of which was covered with paper, and were observed during one hour, paying attention only to the number of yawns. Two drugs influencing serotonergic synapses were used: Lu 10-171, 1-(3-dimenthyl-amino) propyl)- 1 -(p-fluorophenyl)-5-phtalancarbonitrile, (H. Lundbeck and Co.) and metergoline (Farmitalia). Lu 10-171 (citalopram DCI) is a very potent and selective serotonin (5-HT) uptake inhibitor. Some evidence indicates that metergoline blocks selectively central 5-HT receptors. All drugs were dissolved in saline (0.9% NaCI) in such a way that the total volume to be injected was equivalent to 0.01 ml/kg bodyweight. Controls received IP injections of the same volume of saline.

Results and discussion : Infant rats injected with citalopram, in doses ranging from 0.1 to 10 mg/kg, do not exhibit any noteworthy changes in overt behavior. If 40 min later they receive physostigmine (0.15 mg/Kg) the latter drug's yawning inducing effect is strongly potentiated. The effect is statistically significant with citalopram doses from 0.5 mg/kg tipwards, reaching a four to eight-fold increase in mean yawning frequency with the higher doses.

Similar results, but at a lower level of basal yawning frequency, were observed in young (45-day-old) male rats, injected with citalopram, in doses of 5 to 10 mg/kg, the results being statistically significant for the latter dose (MannWhitney U Test, p<0.05).

The potentiating effect of citalopram on physostigmine induced yawning is counteracted by metergoline (5 mg/Kg) when metergoline is injected IP 30 min before receiving citalopram, that is, 70 min before the yawning test with physostigmine. It may be seen that metergoline also reduces the number of yawns induced by physostigmine in the control group, an effect which even if not statistically significant suggests the existance of a basal serotonergic tone favouring the expression of cholinomimetically induced yawning. This suggestion was strengthened by the results of an experiment with a higher dose of metergoline (10 mg/kg), with which the mean yawning level after physostigmine was decreased to only 3 yawns/hour, that is, to 20 percent of the original level, a result which is highly significant (p<0.001, MannWhitney U test).

As citalopram is a very selective inhibitor of the 5-HT reuptake mechanisms, practically devoid of inhibitory effects on NA reuptake or on monoamine oxidase, and has only very weak anticholinergic and antihistaminergic properties, its potentiating effect on physostigmine-induced yawning may reasonably be ascribed to an increase of serotonin in central nervous system synapses somehow related to the cholinosensitive structures responsible for yawning. The effect of serotonin at this level seems to be only positively modulatory, because no yawning has been observed by the administration of citalopram alone. This interpretation is supported by the blocking effect of metergoline, both on the yawning-potentiating effect of citalopram and on the yawning-inducing effect of physostigmine, metergoline being a quite selective blocking agent of serotonin receptors.

  1. Cohen AL Fluoxetine-induced.yawning and anorgasmia reversed by cyproheptadine treatment. J Clin Psychiatry 1992;53:174.
  2. Modell JG. Repeated observations of yawning, cliteral engorgement, and orgasm associated with fluoxetine administration. J Clin Psychopharmacol 1989;9W3-5.
  3. Kimura H, Yarnada K, Nagashima M, Furukawa T. Involvement of catecholamine receptor activities in modulating the incidence of yawning in rats. Pharmacol Biochem Behav 1996;53:1017-21
  4. Kimura H, Yamada K, Nagashima M, Matsumoto S, Ishii Y, Yoshida S, Fujii K, Furukawa T Role of adrenergic neuronal activity in the yawning induced by tacrine and NIK-247 in rats.Pharmacol Biochem Behav 1992 Dec;43(4):985-91
  5. Beale MD, Murphree TM Excessive yawning and SSRI therapy. Int J Neuropsychopharmacol 2000 Sep;3(3):275-276
  6. Urba-Holmgren R, Holmgren B, Rodriguez R, Gonzalez RM Serotonergic modulation of yawning Pharmacol Biochem Behav 1979 Sep;11(3):371-2
  7. observation personnelle
  8. Klein DF. J Repeated observations of yawning, clitoral engorgement, and orgasm associated with fluoxetine administration. Clin Psychopharmacol 1989 Oct;9(5):384