Yawning in male rats is a behavior that may
be induced by a group of dopamine receptors when
low doses of dopamine-receptor agonists are
administered. To determine whether agonist
treatments during postnatal development could
produce a long-lived supersensitization of these
dopamine receptors, rats were treated daily for
the first 28 days from birth with quinpirole HCl
(3.0 mg/kg/day, IP), an agonist that acts at D2
and D3 receptors. At 8 to 10 weeks from birth
the dose-effect curve for quinpirole-induced
yawning demonstrated that a supersensitization
of dopamine receptors for yawning behavior had
occurred. Yawning at the optimal dose of
quinpirole HCl (100 microgram/kg, IP) was
increased 2-fold. The Bmax and Kd for D2
receptor binding in rat striatum were unaltered
in this group of rats. These findings indicate
that dopamine receptors can be ontogenically
"primed" or supersensitized, and that the
phenomenon apparently is not related to changes
in striatal D2 receptor binding
characteristics.
YAWNING is a behavior that can be induced by
a variety of substances, including dopamine D2
receptor agonists and mixed DIM agonists.
Generally, as the dose of agonist increases,
yawning response rate decreases so that a
bell-shaped dose-effect curve for the yawning
response is typically observed. At least part of
the explanation for this effect is that higher
doses of agonists induce competing behaviors,
including the stereotyped actions that are
commonly associated with such agonists. Since
there are few competing behaviors with low doses
of dopamine receptor agoists, yawning represents
a behavior that offers advantages over others
when studying the phenomenon of receptor
supersensitization.
In rats with lesions of brain
dopamine-containing neurons, prolonged dopamine
receptor supersensitization can result (2,19).
However, other treatments and procedures are
associated with temporary changes in dopamine
receptor sensitization.
Because of the finding that neonatal
treatments with dopamine Dl and D2 receptor
antagonists produced an impaired development of
striatal Dl and D2 receptors respectively
(8,15), it was expected that postnatal
treatments with a dopamine receptor agonist
would increase receptor number and/or alter the
sensitivity of the receptor. Also, such an
effect was expected to be long-lived, as per
those after Dl and D2 antagonist treatments.
Yawning was the candidate behavior for
demonstrating this effect, because of the
reasons described above.
This paper describes the production of a
long-lived supersensitization of dopamine
receptors that mediate yawning behavior.
Although the exact class of dopamine receptor
involved with the behavioral event is not known
with certainty, it is shown that the binding
characteristics of dopamine D2 receptors in the
striatum are not altered by these
treatments.
RESULTS AND DISCUSSION
In 8- to 10-week-old male rats that were
treated with quinpirole HCI for the first 28
days from birth, the number of yawns was not
different from that of the vehicle group during
the 60min interval after an injection of saline.
Each group had a mean incidence of yawning in
this instance of less than 1. A challenge dose
of quinpirole increased yawning behavior in both
groups of rats. The maximal incidence of yawning
in both groups occurred at a dose of quinpirole
HCl of 100 g/kg. However, quinpirole-induced
yawning was increased to a much greater extent
in the group of rats that was ontogenically
primed (p<O.OS). For this group yawning was
greater at each different challenge dose of
quinpirole HCI (25 to 200 µg/kg, IP), vs.
the vehicle group (p<O.OS, Fig. 1). The 200
µg/kg dose of quinpirole HCI produced less
yawning than the 100 µg/kg dose, indicating
the bell-shaped curve previously noted by others
for quinpirole-induced yawning in control rats.
The total number of yawns induced by the optimal
dose of quinpirole (100 µg/kg) in the
quinpirole-primed rats (this report) is greater
than that observed previously after dopamine
agonist treatment of rats. In the present study,
as in the above cited reports, more than 90% of
yawns occurred during the first 30 min after
agonist treatment (data not shown). These
findings demonstrate that the absolute maximal
score for yawning behavior can be enhanced in a
specified time frame, thereby providing further
evidence for supersensitization of those
dopamine receptors that mediate the yawning
response.
Despite the increased sensitivity of
ontogenically primed rats for quinpirole
induction of yawning, there was no change in
either the Bmax or Kd for binding to the D2
receptor in rat striatum. Therefore,
sensitization appears to be a phenomenon not
related to the number or affinity of D2
receptors. It is likely that mechanisms
associated with generation of second messengers
are more relevant in mediating the
supersensitive phenomenon. However, it is
possible that a different class of receptors,
namely the D3 subgroup, may be involved in
mediating yawning behavior per se, and the
supersensitization of this behavior. This view
is supported by the fact that quinpirole is 100
times more selective for D3 than D2 receptors.
Specific agonists and antagonists for the D3
receptor are not yet available to resolve this
hypothesis.
In summary, we have produced a rat model
with a long-lived supersensitization of dopamine
receptors that is associated with yawning
behavior. This model may be of value in the
study of both behavioral and biochemical
processes related to supersensitization of
receptors.
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