It is known that dopamine (DA) receptors can
be sensitized by repeated treatments with
quinpirole during postnatal development. This
study was undertaken to determine whether
low-dose quinpirole treatments might sensitize
receptors to quinpirole-induced yawning
behavior. Rats were treated with quinpirole HCl
(50 micrograms/kg per day) or saline at four
different periods of ontogeny: a) the 10th day
of gestation to day of birth; b) 1st-11th days
after birth; c) 12th-22nd days from birth; or d)
23rd-33rd days from birth. The numbers of yawns
occurring in 1 h after a challenge dose of
quinpirole HCl (50 micrograms/kg, IP) was
determined at 6 weeks. Rats exposed prenatally
to quinpirole demonstrated increased numbers of
yawns following the third dose of quinpirole
(2-day interval between doses). In rats exposed
postnatally to quinpirole, there was a 70-300%
increase in the yawning response, with the
greatest response occurring in the group treated
with quinpirole from birth to 11 days from
birth. The findings demonstrate that quinpirole
receptors are sensitized by a low dose of
quinpirole, 60-fold lower than previously shown.
It is suggested that sensitized receptors are of
the DA D3 subclass.
DOPAMINE (DA) agonists are known to induce
yawning behavior in male rats. Because D3
receptors have 113-fold greater affinity for
quinpirole, and because low doses of quinpirole
induce yawning behavior, it has been postulated
that D3 receptors are responsible for DA
agonistinduced yawning behavior.
Recently, we found that ontogenic treatments
with the DA agonist quinpirole would sensitize
receptors to quinpiroleinduced yawning responses
in adulthood. The current study was conducted to
determine whether low doses of quinpirole during
ontogeny would sensitize receptors to
quinpirole-induced yawning behavior later in
life.
DISCUSSION
These findings demonstrate several features
relevant to DA receptors of the D2 class (i.e.,
D2, D3, and D4 receptors). First, DA receptors
of the D2 class can be sensitized during
development by treatments with quinpirole. This
is in accord with previous demonstration of this
phenomenon. A second, and the most important,
feature is that low doses of quinpirole can
produce this effect. The dose used in this study
is 60 times lower than that used in our previous
study. This also is in accord with the
suggestion that the yawning response may be a DA
D3-mediated event because D3 receptors have an
affinity for quinpirole that is 113 times
greater than shown specifically for D2
receptors.
Another aspect is that quinpirole treatments
will sensitize to yawning responses when low
doses of this substance are administered for
only 11 consecutive days, even as late as 33
days from birth. However, the greatest effect is
produced when quinpirole is administered during
the first 11 days from birth.
Finally, the effects of quinpirole may be
latent, as shown for prenatally exposed rats.
Only after several treatments with quinpirole at
6 weeks did sensitivity occur. The phenomenon
whereby repeated exposure to an agonist induces
receptor sensitivity is known as priming. It is
well described for DA D1 receptors. Because
quinpirole is able to cross the bloodbrain
barrier, it was assumed that this agonist would
cross the placental barrier. We have no direct
measure of this, but the findings give credence
to this likelihood.
The present findings demonstrate that
quinpirole receptors can be primed or sensitized
by low-dose quinpirole treatments and the type
and magnitude of the effect is dependent upon
the period of exposure to quinpirole during pre-
or postnatal development of male rats.
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