mise à jour du
3 juillet 2006
Pharmacol Biochem Behav
Low-dose quinpirole ontogenically sensitizes
to quinpirole-induced yawning in rats
Kostrzewa RM, Brus R.
Department of Pharmacology, James H. Quillen College of Medicine, East Tennessee State University, Johnson City USA
Drinking sucrose or saccharin enhances sensitivity of rats to quinpirole-induced yawning. Serafine KM


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.
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.
Mogilnicka E, Klimek V Drugs affecting dopamine neurons and yawning behavior. Pharmacol Biochem Behav 1977; 7; 303-305
R Brus , R Szkilnik, RM Kostrzewa Nitric oxide (NO) and central dopamine (DA) D3 receptor reactivity to quinpirole in rats Act Neurobiol Exp 1996; 56; 15-19
Kostrzewa RM and R Brus Is dopamine-agonist induced yawning behavior a D3 mediated event? Life Sci 1991; 48; 26; 129
Kostrzewa RM, Brus R. Ontogenic homologous supersensitization of quinpirole-induced yawning in rats. Pharmacol Biochem Behav. 1991;39(2):517-519.
Kostrzewa RM, Brus R, Rykaczewska M, Plech A. Low-dose quinpirole ontogenically sensitizes to quinpirole-induced yawning in rats. Pharmacol Biochem Behav. 1993;44(2):487-489.
Eguibar JR et al Behavioral differences between selectively bred rats: D1 versus D2 receptors in yawning and grooming Pharmacology; Biochemistry and Behavior 2003; 74; 827-832
Spina, R Longoni, A Mulas, G di Chiara SKF 38393 potentiates yawning induced by LY 171555: further evidence against the autoreceptor hypothesis of yawning Psychopharmacology 1989; 98; 567-568
Oswiecimska J, Brus R, Szkilnik R, Nowak P, Kostrzewa RM 7-OH-DPAT, unlike quinpirole, does not prime a yawning response in rats Pharmacol Biochem Behav. 2000; 67; 11-15
Nowak P, Labus L, Kostrzewa RM, Brus R. DSP-4 prevents dopamine receptor priming by quinpirole Pharmacol Biochem Behav. 2006;84(1):3-7