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.
[...]
Discussion
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