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La parakinésie brachiale oscitante
Yawning: its cycle, its role
Warum gähnen wir ?
 
Fetal yawning assessed by 3D and 4D sonography
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Le bâillement, du réflexe à la pathologie
Le bâillement : de l'éthologie à la médecine clinique
Le bâillement : phylogenèse, éthologie, nosogénie
 Le bâillement : un comportement universel
La parakinésie brachiale oscitante
Yawning: its cycle, its role
Warum gähnen wir ?
 
Fetal yawning assessed by 3D and 4D sonography
Le bâillement foetal
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mystery of yawning 

 

 

 

 

 

 

 

 

 

 

 

 

mise à jour du
3 janvier 2014
Eur J Pharmacol
1994;254(1-2):91-96
Effects of apomorphine, physostigmine and vasoactive intestinal peptide on penile erection
and yawning in diabetic rats
 
Yamaguchi Y, Kobayashi H
 
Research Laboratory, Zenyaku Kogyo, Tokyo, Japan
 

Chat-logomini

Abstract
 
The present report describes for the first time the effects of systemic administration of apomorphine and of physostigmine, as well as the effects of central and systemic administration of vasoactive intestinal peptide (VIP), on penile erection and yawning in rats with streptozotocin-induced diabetes. Systemic administration of apomorphine induced both penile erection and yawning in non-diabetic rats but not in diabetic rats, while that of physostigmine induced only yawning in non-diabetic rats, and neither yawning nor penile erection in diabetic rats. Intracerebroventricular administration of VIP induced both penile erection and yawning in non-diabetic rats, but neither was induced in diabetic rats. Application of VIP as an ointment to the surface of the glans penis induced penile erection but not yawning in both non-diabetic and diabetic rats. Thus, penile erection and yawning are less easily induced in diabetic rats than in non-diabetic rats. Grooming occurred whenever penile erection was induced, but was not associated with yawning.
 
 
1. Introduction
 
Systemic injection of apomorphine, a dopamine agonist, has been reported to induce yawning (Mogilnicka and Klimek, 1977; Holmgren and Urba-Holmgren, 1980) and both penile erection and yawning in rats (Gower et al., 1984; Holmgren et al., 1985). Physostigmine, an inhibitor of acetylcholinesterase, induced only yawning when administered systemically (Urba-Holmgren et al., 1977; Holmgren and Urba-Holmgren, 1980; Yamada and Furukawa, 1980), but not penile erection (Gower et al., 1984). Pilocarpine, an acetylcholine agonist, induced penile erection (Maeda et al., 1990) and yawning (Yamada and Furukawa, 1980).
 
In addition to drugs that act via dopaminergic and cholinergic mechanisms, peptidergic mechanisms are also involved in both penile erection and yawning: adrenocorticotropin (ACTH) and melanocyte-stimulating hormone (MSH) were active in several species of mammals (see Bertolini and Gessa, 1981, for review), and oxytocin was active in rats (Argiolas et al., 1985, 1986). Vasoactive intestinal peptide (VIP) seems to participate in penile erection: during erection, plasma VIP levels in the penile circulation were markedly elevated in man (Virag et al., 1982; Ottesen et al., 1984) and injection of VIP into the cavernous space stimulated penile erection in man (Ottesen et al., 1984; Kiely et al., 1989). Furthermore, in rats, systemic administration of VIP increased the rate of copulation and decreased the time to the first intromission. An antagonist of VIP, a peptide of 28 amino acids composed of a portion of VIP and a portion of neurotensin, inhibited these sexual events (Gozes et al., 1989). In these latter studies, yawning after administration of VIP was not recorded. The various reports together suggest that dopaminergic, cholinergic and peptidergic nerves are involved in the induction of penile erection and/or yawning. However, the interrelation between these three classes of nerves has not been elucidated.
 
Penile dysfunction is a common complication of diabetes mellitus (Rubbin and Babbott, 1958; Sch6ffling et al., 1963; Ellenberg, 1971) and the prevalence of impotence among diabetic men is high (Kolodny et al., 1973). Lincoln et al. (1987) observed that numbers of fibers showing VIP-like immunoreactivity and the intensity of staining for acetylcholinesterase activity were markedly reduced, as were contents of noradrenaline, in penile tissues of diabetic men. They concluded that VIPergic, cholinergic and adrenergic nerves in the penis are affected in diabetes mellitus and, thus, dysfunction of the nerves contributes to the development of impotence in diabetic men. In diabetic rats, a reduction in sexual behavior, such as ejaculations, mounting or intromissions, was demonstrated by Fernandez-Collazo and Foglia (1970). However, Sachs et al. (1982) found that none of the measures of sexual behavior, such as sexual motivation, performance or penile responsiveness, was depressed in diabetic rats. It is not clear whether diabetic rats possess normal potency with regard to penile erection and yawning. Furthermore, as far as we know, there have been no experiments dealing with penile erection and yawning in relation to VIP in diabetic rats.
 
The present study was designed to examine the involvement of dopaminergic, cholinergic and VIPergic mechanisms in penile erection and yawning, and to explore the functional relationship between the mechanisms in non-diabetic and diabetic rats. The occurrence of grooming was also noted during the course of this study.
 
4. Discussion
 
In the present experiments, systemic administration of apomorphine induced penile erection and yawning in non-diabetic rats, as reported by Gower et al. (1984), Holmgren et al. (1985), Melis et al. (1987, 1989) and Argiolas et al. (1987), and systemic administration of physostigmine induced only yawning in non-diabetic rats, as shown by Gower et al. (1984). Therefore, it is apparent that penile erection and yawning induced by apomorphine are mediated by dopaminergic nerves and yawning induced by physostigmine is mediated by cholinergic nerves. It has been demonstrated that apomorphine- induced yawning (Yamada and Furukawa, 1980) and penile erection (Maeda et al., 1990), as well as physostigmine-induced yawning (Yamada and Furukawa, 1980), can be completely inhibited by scopolamine, a muscarinic receptor antagonist, but not by methylscopolamine. These observations suggest that dopaminergic mechanisms involved in penile erection and yawning are under the control of cholinergic nerves in the brain.
 
In diabetic rats, apomorphine failed to induce penile erection and yawning, and physostigmine failed to induce yawning. Lozovsky et al. (1981) reported that, in streptozotocin-treated diabetic rats, there were changes in the sensitivity of postsynaptic dopamine receptors in the brain. Welsh and Wecker (1991) observed a significant reduction in the rates of synthesis and release of acetylcholine by striatal slices from streptozotocintreated diabetic rats. These dopaminergic and cholinergic dysfunctions might have been causes of the insensitivity to apomorphine and physostigmine, resulting in impotence of diabetic rats. We found that i.c.v, injection of VIP induced penile erection and yawning in non-diabetic rats. Itoh et al. (1988) reported that injection (i.c.v.) of VIP facilitated the metabolism of dopamine in various regions of the rat brain and Luine et al. (1984) reported that addition of VIP to brain homogenates of the hypothalamus and the hippocampus increased choline acetyltransferase activity. Thus, induction of penile erection and yawning by VIP (i.c.v.) may be due to activation of dopaminergic and/or cholinergic systems in the brain. In diabetic rats, injection (i.c.v.) of VIP failed to induce either penile erection or yawning. It is likely that VIP was not sufficiently stimulatory to induce penile erection and yawning in diabetic rats with dopaminergic (Lozovsky et al., 1981) and cholinergic (Welsh and Wecker, 1991) dysfunction.
 
It should be noted here that apomorphine interacts with postsynaptic dopamine receptors in the paraventricular nucleus, with a resultant release of oxytocin (Melis et al., 1989), which is known to induce penile erection and yawning (Argiolas et al., 1985, 1986). Furthermore, VIP-immunoreactive neurons can be found in the paraventricular nucleus (Ceccatelli et al., 1989). Therefore, there is a possibility that induction of penile erection and yawning by i.c.v. VIP is mediated via oxytocin. Neural relationships between VIP, ACTH and MSH (see Bertolini and Gessa, 1981, for review) in the induction of penile erection and yawning are not known at present.
 
Dermal application of VIP induced penile erection but not yawning in both diabetic and non-diabetic rats. Yawning seems to be induced only through activation of the central nervous system. It has been demonstrated that VIP, injected into the cavernous space, induces penile erections in men (Ottesen et al., 1984; Kiely et al., 1989), and that topical application of a conjugate of VIP and stearic acid (stearyl-VIP) to the sex organ significantly stimulates sexual behavior (copulation rate) and penile reflexes (erection) in testosterone-treated castrated rats (Gozes and Fridkin, 1992). Dermal application or intracavernous injection of VIP may result in a direct action on blood vessels, since VIP nerve terminals are found densely distributed around penile erectile tissue (Polak et al., 1981; Dail et al., 1983). Therefore, it is likely that a reduction in the number of VIP-immunoreactive nerves in the penis of diabetic rats (Crowe et al., 1983) may be one of the causes of impotence in these rats. Grooming occurred whenever a penile erection was induced in the present experiments, as previously reported with apomorphine (Melis et al., 1989), ACTH and MSH (see Bertolini and Gessa, 1981, for review). There seems to be some neural relationship between grooming and penile erection but it remains to be characterized. Grooming has no relationship to yawning, since yawning induced by physostigmine was not accompanied by grooming.