- INTRODUCTION
- In our laboratory we obtained two inbred
sublines of Sprague-Dawley rats that differ in
their spontaneous yawning frequency
(Urba´-Holmgren et al., 1990). The
High-Yawning (HY) subline has a mean of 20 yawns
per hour, and the Low-Yawning (LY) subline has
an average of 2 yawns/hour (Urba-Holmgren et
al., 1990; Eguibar et al., 2003).
-
- A yawn is a phylogenetically old,
stereotypic event that occurs alone or
associated with other behavior such as grooming
or penile erection and in different
environmental conditions (Anias et al., 1984;
Baenninger and Greco, 1991;Holmgren et al.,
1991; Argiolas and Melis, 1998; Eguibar et al.,
2004).
-
- The physiological function of yawning is
still unknown; however, it is clear that several
neurotransmitters participate in its regulation.
Among them, the best known are dopamine (DA),
acetylcholine, and several neuropeptides such as
ACTH1Ð24, a-MSH, endorphin, oxytocin, and
prolactin (for a review, see Argiolas and Melis,
1998).
-
- Some studies examined the participation of
the nigrostriatal or mesolimbic dopaminergic
systems (Dourish and Hutson, 1985; Stoessl et
al., 1987; Stahle and Ungersted, 1990). DA
receptors are classified into two broad
families, the D1-like (D1 and D5) and D2-like
(D2, D3, and D4) receptors (Gingrich and Caron,
1993; Niznik and VanTol, 1992; Sibley and
Monsma, 1992). Both the D1 and the D2 receptors
are abundantly expressed and widely distributed
throughout striatal and limbic dopamine fields,
including the nucleus accumbens,
caudate-putamen, and the olfactory tubercle
(Flores et al., 1996).
-
- It is well known that the activation of the
D2 receptors by apomorphine, (Ð)-3-PPP (3-
(3-hydroxyphenyl)-N-propylpiperidine
hydrochloride), and quinpirole induce yawning
(Mogilnicka and Klimek, 1977; Holmgren et al.,
1980; Yamada and Furukawa, 1980, Stahle, 1992;
Eguibar et al., 2003). Lesions with 6-OH-DA in
the nigrostriatal pathway abolished dopaminergic
yawning (Dourish and Hutson, 1985; Yamada et
al., 1986; Stoessl et al., 1987; Stahle and
Ungersted, 1990). In addition, yawning induced
by apomorphine can be blocked by the D1
antagonist SCH 23390 (Code and Tang, 1991).
-
- The DA D1 agonist SKF 38393 decreases
yawning but increases grooming in HY rats
compared to LY rats, but quinpirole produced a
higher yawning frequency in HY than in LY rats
(Eguibar et al., 2003). HY rats have a higher
score of grooming bouts in a novel environment
and after wetting the fur (Eguibar and Moyaho,
1997; Moyaho et al., 1995).
-
- Therefore, both DA receptors have been
proposed to participate in the control of
yawning and grooming behavior. Our
pharmacological reports strongly suggest
differences in the effects of dopaminergic
induced behaviors in HY compared to LY rats.
Taking into account such differences, in the
present study we compared the regional
distribution of the DA receptor subtypes,
D1-like and D2-like, and the DA transporter in
the caudate-putamen and mesolimbic areas between
adult male HY and LY rats using
autoradiography.
-
- DISCUSSION
- In the present study we found that HY rats
have higher levels of DA D1-like receptors in
some subregions of the caudate-putamen, such as
the dorsomedial, ventral, and fundus compared to
LY rats, whereas the DA D2-like receptor and DA
transporter levels were not significantly
different between either subline in any
subregion measured.
-
- Previous findings indicated that DA D1-like
receptors are implicated in yawning and grooming
behaviors (Ferrari and Mangiafico, 1988;
Berridge and Aldrich, 2000a,b). Pharmacological
data from our laboratory and our recent report
suggest that HY and LY rats have an altered DA
function at the level of the nigrostriatal DA
system compared with outbred Sprague-Dawley rats
(Urba-Holmgren et al., 1993; Eguibar et al.,
2003).
-
- Furthermore, differences in the receptor
levels would imply differences in genetic
elements regulating receptor expression, which
therefore explains the different expression of
behavior in the mediated limbic or nigrostriatal
pathways, and so could beinvolved in
quantitative differences in yawning and grooming
in HY and LY rats. The HY rats exhibit higher
spontaneous yawning frequency (Urba-Holmgren et
al., 1990) and also show higher incidences of
yawning after systemic administration of DA D2
agonists (Urba-Holmgren et al., 1993; Eguibar et
al., 2003).
-
- However, HY rats also have a higher
incidence of grooming bouts after systemic
injection of SKF 38393, a DA D1 agonist.
However, quinpirole, a DA D2 agonist,
coadministered with SKF-38393, a DA D1 agonist,
did not potentiate the yawning-induced by
quinpirole (Eguibar et al., 2003), whereas the
activation of just the DA D1 receptors by SKF
38393 produced a decrease in the yawning
behavior more markedly in HY than in LY rats
(Eguibar et al., 2003). However, some reports
proposed that the coactivation of dopamine D1
and D2 receptors is necessary to induce yawning
(for review, see Beninger et al., 1991). Yawning
is a typical dopaminergic autoreceptor-mediated
response (Stahle and Ungersted, 1986).
-
- The activation of the DA D3 receptor is
quite effective in eliciting yawning (Kostrzewa
and Brus, 1991; Damsma et al., 1993). We have
preliminary results that suggest a major
participation of the DA D3 receptors in the
yawning behavior of the HY compared to LY rats
(M. Dõ´az-Romero and J.R. Eguibar, unpubl.
data).
-
- The caudate-putamen is the main nucleus of
the basal ganglia with the highest level of DA
D1-like and D2-like receptors (Flores et al.,
1996, 2002). Moreover, the caudate-putamen
nucleus is a key element in the generation and
maintenance of the grooming syntactic chain
(Berridge et al., 2000a). The multiunit
recording of single neurons, from the
dorsolateral part of the caudate- putamen
nucleus, shows an increase of their activity
during the initial phase of the syntactic
grooming chain (SGC), but not in other related
areas, indicating the importance of the
caudate-putamen in initiating sequential
behaviors (Berridge and Fentress, 1987).
Bilateral lesions in the rostral dorsolateral
part of the caudate-putamen produced impairment
of SGC in the rat (Cromwell and Berridge,
1996).
-
- However, bilateral lesions in the
dorsomedial, ventromedial, or ventrolateral part
of the caudate-putamen did not impair
organization of the syntactic grooming chain
(Berridge and Whishaw, 1992). In fact, the
systemic or intraventricular administration of
SKF 38393, a D1 agonist, increased the ability
to initiate SGC but not to complete it (Berridge
and Aldrich, 2000a,b). In addition, the
intraventricular administration of SKF 82958, a
full D1 agonist, increased the total of grooming
behavior; however, it was not changed by SKF
38393, indicating a complex participation of
postsynaptic dopaminergic receptors in the
regulation of grooming (Berridge and Aldrich,
2000b).
-
- These results also demonstrate that
dopaminergic neurotransmission in the
nigrostriatal pathway is a key element in the
expression of SGC. The higher expression of
grooming behavior of HY compared to LY rats
under different conditions could be caused by,
at least in part, a higher number of DA D1-like
receptors in the caudate-putamen, as shown in
this report. Systemic D1 agonists induced a
greater number of grooming bouts in HY compared
to LY rats (Eguibar et al., 2003). Grooming
bouts are also more numerous in HY rats after
water immersion.
-
- These bouts are disorganized and have a low
mean duration but higher frequency, indicating
greater perseverance in cleaning behavior in HY
than in LY rats (Moyaho et al., 1995; Eguibar
and Moyaho, 1997). The perseverance in the
cleaning behavior is suggestive, in some ways,
of an obsessive-compulsive disorder (OCD),
because OCD patients frequently show
perseverance in cleaning activities, have
alterations in the caudate nucleus (Rapoport,
1989), and are treated with dopaminergic
antagonists, supporting the participation of the
dopaminergic system in this illness. Further
experiments will help to elucidate the specific
role of dopaminergic receptors in OCD and in
grooming behavior in HY rats.
-
- In summary, our findings provide additional
evidence that an increase in the DA transmission
via DA D1-like receptors in the caudate-putamen
in HYrats may be in part be related to the
increase in the grooming behavior exhibited by
this inbred Sprague- Dawley subline of
rats.
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