mise à jour du
1 janvier 2004
Pharmacology & toxicology
Effects of lead exposure on licking and yawning behaviour in rats (saturnism)
M Ghazi-Khansari, N Rezvani, S Bani-Assadi, MR Zarrindast
Department of Pharmacology, School of Medicine
Tehran University of Medical Sciences, Tehran, Iran
Index de tous les travaux de MR Zarrindast


The yawning behaviour is a strange and poorly understood response induced in many vertebrate species (Baenninger 1987). The involvement of central cholinergic (UrbaHolmgren et al. 1977; Yamada & Furukawa 1980; Ushijima et al. 1984, Zarrindast & Poursoltan 1989) and dopaminergic systems (Mogilnicka & Klimek 1977; Baggio & Ferrari 1983; Zarrindast & Poursoltan 1989) in yawning behaviour has been established. Septal and striatal dopamine receptors have been proposed to be involved in yawning behaviour in rats (Yamada et al. 1986). The behaviour seems to be mediated through D2 dopamine receptor in rats (Protais et al. 1983; Gower et al. 1984; Longoni et al. 1987; Zarrindast & Poursoltan 1989).
Mesolimbic and nigrostriatal dopaminergic pathway may be important in the mediation of locomotor activity and stereotyped behaviours. Locomotion has been related to nucleus accumbens (Jackson et al. 1975), whereas stereotyped behaviours (e.g. head movement, licking and localized sniffing) are more closely associated with the caudate striatum (Kelly et al. 1975).
Lead exposure is still one of the most important health hazards to human, and in particular to children as due to their enhanced sensitivity of developing nervous system, they are more susceptible to lead exposure (Mushak et al. 1989). Lead exposure has been reported in animal experiments (Murayama et al. 1990). It has also been shown that lead is capable of affecting dopamine receptor subtypes (Moresco et al. 1988). Further, lead exposure also has been found to produce functional dopaminergic supersensitivity which involves both the D1 and D2 receptor subtypes (Cory-Slechta & Widzowski 1991) and alteration of synthesis of dopamine in the rat brain (Govoni et al. 1979). With a view to the above reports on the effects of lead on behaviour, the present study was undertaken to investigate the effects of lead exposure on yawning and licking behaviour induced by dopaminergic and cholinergic agents. [...]
Our previous study showed that dopaminergic receptor stimulation produces yawning (Zarrindast & Poursoltan 1989), sniffing (Zarrindast & Naghashi 1991) and licking (Zarrindast et al. 1992; Zarrindast & Sharifzadeh 1995) behaviour in rats.
The present study was designed to examine the effect of subchronic exposure of lead on licking induced by apomorphine, and yawning induced by bromocriptine and physostigmine.
Dopamine receptors in the central nervous system have been classified into D1 and D2 receptor subtypes (Kebabian & Caine 1979), with D1 receptors being positively linked to adenyl cyclase and D2 receptors being negatively linked (or not linked) to adenylcyclase. These two types of receptors represent distinct molecular entities (Nielsen et al. 1984), and different distribution in the brain (Altar et al. 1985; Martres et al. 1985).
The present data show that the dopamine receptor agonist apomorphine (Seeman 1980) induced dose-dependent licking in rats, which agrees with our previous reports (Zarrindast et al. 1992; Zarrindast & Sharifzadeh 1995).
Our data also indicate that lead exposure at different concentrations significantly increased licking induced by apomorphine. The concentration of 0.025% of lead in drinking water increased the abnormal behaviour after 28 days exposure. However higher concentration (0.05%) of lead increased the abnormal behaviour after 7 days exposure. Our previous results indicate that longer exposure to lead would cause increase in the blood lead level (GhaziKhansari et al. 1997), which may indicate a leadpeak concentration was necessary to influence the yawning and licking behaviours. D1 and D2 dopaminergic mechanism(s) have been shown to be involved in licking behaviour (Zarrindast et al. 1992; Zarrindast & Sharifzadeh 1995). Since apomorphine has also D1/D2 dopamine receptor agonist properties (Seeman 1980), it may be suggested that this metal at least influences one of the dopamine receptors indicated. Our results seem to support these of Moresco et al. (1988) who suggested that chronic lead exposure may increase the number of D2 receptors in the striatum of rat offspring, if the mothers had consumed lead chronically However, not only was the lead exposure in our experiment lower (one tenth to one fifth), but we also used subchronic lead exposure in adult male rats.
Our present results show that lead exposure is able to decrease yawning behaviour in rats induced by the D2 receptor agonist bromocriptine and anticholinesterase. Yawning behaviour is mediated via a D2 dopamine autoreceptor (Yamada et al. 1986; Zarrindast & Poursoltan 1989). Our present results may be supported by data by other scientists who showed that both yawning and penile erection are induced by D2 receptor stimulation (Argiolas et al. 1987; Zarrindast & Poursoltan 1989; Melis et al. 1987; Gower et al. 1984) and that lead exposure can decrease penile erection induced by D2 receptor activation (Ghazi-Khansari et al. 1997). Supersensitivity of D2 dopamine receptors has been reported with the same level of lead exposure by CorySlechta & Widzowski (1991). Since yawning behaviour can be induced by stimulation of presynaptic D2 dopamine receptors (Zarrindast & Poursoltan 1989), mediation of lead response through presynaptic D2 receptor activation seems unliklely.
Since yawning induced by dopaminergic agents may be mediated through cholinergic mechanisms (Zarrindast & Poursoltan 1989), and lead exposure also decreased yawning induced by physostigrnine, it may be possible that the lead effect on yawning induced by both bromocriptine and physostigmine be mediated via influence of lead on the cholinergic system. A previous report indicates that chronic lead exposure significantly inhibits the availability of choline for synthesis of acetylcholine in the synaptosome (Silbergeld & Goldberg 1975). Moreover other researchers reported that lead appears to displace calcium in presynaptic sites, thereby affecting the release of acetylcholine or uptake of choline, and thereby decreasing acetylcholine release (Carroll e t al. 1977; Silbergeld 1977; Silbergeld & Adler 1977). Although subchronic lead exposure was employed in our study, the possibility exists that reduction in yawning be due to the above mechanisms