mystery of yawning
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Fetal yawning assessed by 3D and 4D sonography
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Le bâillement : de l'éthologie à la médecine clinique
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 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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mise à jour du
20 février 2011
European Journal of Pharmacology
1997;271:253-257
Old rats are unresponsive to the behavioral effects
of adrenocorticotropin
Rosanna Poggioli Augusta Benelli, Rossana Arletti, Anna Valeria Vergoni, Barbara Menozzi, Alfio Bertolini
 
Department of Biomedical Sciences, Section of Pharmacology, University of Modena, Italy

Chat-logomini

 
Abstract
 
In 28 month-old male rats, the i.c.v. injection of adrenocorticotropin [ACTH-(1-24)} (4 pg/rat) did not induce the typical behavioral syndrome (excessive grooming, stretching, yawning, penile erections). This indicates that the behavioral effects of melanocortins are age-dependent, suggesting either an aging-linked impairment of the nervous circuitries involved or a reduction of the number (or affinity, or both) of the brain melanocortin receptors in the elderly
 
1. Introduction
 
In mammals, the administration of melanocytestimulating hormone and of adrenocorticotropin hormone (MSH-ACTH neuropeptides, melanocortins, melanopeptides) into the cerebral ventricles or into selected brain areas induces a complex and unique behavioral syndrome, characterized by compulsive care of body surface (grooming), by repeated episodes of stretching and yawning, and by recurrent episodes of penile erection with ejaculation (the picture induced by pharmacological amounts of melanocortins is a remarkable and curious concentrate of physiologic behaviors) (Ferrari et al., 1955, 1963; Ferrari, 1958; Bertolini and Vergoni, 1968; Bertolini et al. 1969, 1975, 1988; Gispen et al., 1975; Bertolini and Gessa, 1981). Moreover, melanocortins improve short-term memory processes (De Wied, 1964, 1966; De Wied and Bohus, 1966; De Wied and Jolies, 1982), and increase motivation and attention (De Wied, 1965, 1969). Structure-activity studies (Spruijt et al., 1985; De Wied and Jolles, 1982; Eberle, 1988; De Wied and Woiterink, 1988) have shown that these behavioral effects of melanocortins are related to the melanocyte-stimulating, rather than to the adrenocorticotrophic activity of these peptides.
 
A physiological meaning of such effects has been repeatedly suggested (for reviews see: De Wied and Jolies, 1982; De Wied and Ferrari, 1986) and is also strongly supported by the finding that binding sites for melanocortins are found throughout the brain (Tatro, 1990; Mountjoy et al., 1992).
 
Adequate brain cholinergic activity is required for the display of the melanocortin-induced behavioral syndrome, which is prevented by the i.c.v. administration of hemicholinium-3 (Poggioli et al., 1991).
 
Aging is characteristically associated with progressive impairment of brain cholinergic function (Bartus et al., 1982; Palmer and Gershon, 1990) and stretching, yawning and penile erection are much more frequent in young than in old animals (Preyer, 1923; Lehmann, 1979). In humans, yawning and stretching are already present at birth, and spontaneous penile erections occur very frequently in babies, whereas old people rarely yawn and even more rarely stretch or display full penile erection. Moreover, self-care and body cleaning are often neglected in the old, and deterioration of short-term memory - together with reduced motivation and attention - is typical of aging. These considerations prompted us to study the influence of aging on the behavioral response to melanocortins.
 
4. Discussion
 
These data show that old rats are unresponsive to the behavioral effects of adrenocorticotropin. The i.c.v. injection of ACTH-(1-24) at a dose (4 jig/rat) that is maximally active to induce the most typical behavioral symptoms (excessive grooming, stretchings, yawnings, penile erections) in adult (3- to 4-month-old) animals (Bertolini et al., 1988), has no behavioral activity in 28-month-old rats.
 
Previous data for grooming showed that the level of ACTH-induced excessive grooming in aged rats was not significantly different from that displayed by young animals. However, such data were obtained in 24-
 
month-old rats, and an accurate analysis of grooming activity indicated a loss in sequential organisation of such behavior in aging rats (Spruijt et al., 1988).
 
The loss of behavioral responsivity to ACTH-(1-24) in 28-month-old rats may depend on (i) an aging-linked progressive reduction, and eventual loss, of responsivity of the nervous structures involved in the behavioral effects of melanopeptides; (ii) an aging-linked, progressive impairment of the neurotransmitter systems (typically cholinergic systems) (Poggioli et ai., 1991) involved in the behavioral effects of melanopeptides; (iii) an aging-linked progressive reduction of the production of permissive hormones, typically sexual steroid hormones; however this may be the case only for penile erection, because testosterone plays a fundamental permissive role only for this behavioral effect of melanocortins (Bertolini and Vergoni, 1968); (iv) an aging-linked reduction of the number (or affinity, or both) of brain melanocortin receptors. One possibility does not exclude the others.
 
Melanocortins are well known trophic factors for nervous tissue, and their concentration is significantly reduced in the brain of aging mammals (Barnea et ai., 1982; Bell and Lipton, 1987), as well as in defined brain areas of patients with Alzheimer's disease (Arai et ai., 1986). On the other hand, the highest concentrations of a-MSH are found during fetal life, and this neuropeptide seems to be involved in brain development as injections of a-MSH antisera into the fetal rat produce a decrease in brain weight and a delay in neuron development (for a review see: O'Donohue and Dorsa, 1982; Eberle, 1988), whereas treatment of neonatal rats with MSH peptides improves their performance in learning, memory and attention (Beckwith et al., 1977), accelerates motor behavior and the onset of eye opening (Van de Helm-Hylkema and De Wied, 1976).
 
Melanocortins exert atrophic action on both the central and peripheral nervous system also in adulthood, during nerve regeneration after mechanical lesion (Verhaagen and Gispen, 1988; Gispen, 1990; Strand and Kung, 1980; Bijlsma et al., 1981, 1983, 1984; Saint-Côme et al., 1982; De Koning et al., 1986; Verhaagen at ai., 1986; De Koning and Gispen, 1987) or after lesions of the brain (Nyakas et ai, 1985; Isaacson and Poplawsky, 1983; Benelli et al., 1988). Ischemic injury to brain neurons is attenuated by adrenalectomy - which causes an increased production of melanocortins - and adrenalectomy also prevents the aginglinked loss of central neurons (Sapolsky and Pulsineili, 1985; Sapolsky et al., 1985).
 
Our present data, showing that the brain of old animals is no longer responsive to the behavioral effects of melanocortins - together with the notion that the behavioral signs stimulated by melanocortins are rare in the elderly - suggest that a decreased neuronal responsivity to melanocortins may play some role in the aging-related decline in brain functioning.
 
 
-Poggioli R, Valerja Vergoni A, et al. Influence of clonidine on the ACTH-induced behavioral syndrome, European J. Pharmacol. 1984;101:299-301
-Poggioli R et al Nitric oxide is involved in the ACTH-induced behavioral syndrome Peptides 1995;16(7)1263-1268