Yawning and locomotor behavior induced by dopamine receptor agonists in mice and rats

Abstract

Dopaminergic (DA) agonist-induced yawning in rats seems to be mediated by DA D3 receptors, and low doses of several DA agonists decrease locomotor activity, an effect attributed to presynaptic D2 receptors. Effects of several DA agonists on yawning and locomotor activity were examined in rats and mice. Yawning was reliably produced in rats, and by the cholinergic agonist, physostigmine, in both the species. However, DA agonists were ineffective in producing yawning in Swiss-Webster or DA D2R and DA D3R knockout or wild-type mice. The drugs significantly decreased locomotor activity in rats at one or two low doses, with activity returning to control levels at higher doses. In mice, the drugs decreased locomotion across a 1000-10 000-fold range of doses, with activity at control levels (U-91356A) or above control levels [(+/-)-7-hydroxy-2-dipropylaminotetralin HBr, quinpirole] at the highest doses. Low doses of agonists decreased locomotion in all mice except the DA D2R knockout mice, but were not antagonized by DA D2R or D3R antagonists (L-741 626, BP 897, or PG01037). Yawning does not provide a selective in-vivo indicator of DA D3R agonist activity in mice. Decreases in mouse locomotor activity by the DA agonists seem to be mediated by D2 DA receptors.

Fig. 1

Effects of 7-OH-DPAT and PD 128907 on yawning (top panel) and locomotor activity (bottom panel) in rats. Vertical axes: mean number of yawns in a 60-min observation period (top panel) or locomotor activity counts (bottom panel) during the same observation period. Horizontal axes: drug dose in mg/kg. Vertical bars indicate ± SEM. Each dose was examined in four to six rats. Statistical significance of results versus vehicle controls according to a Dunnett’s test are indicated as follows: *P < 0.05; **P < 0.01. V, vehicle.

Fig. 2

Effects of dopamine agonists on locomotor activity in Swiss–Webster mice. Ordinates: mean number of locomotor activity counts during a 60-min observation period. Horizontal axes: drug dose in mg/kg. Vertical bars indicate ± SEM. Each dose was examined in four to 24 mice. Statistical significance of results versus vehicle controls according to a Dunnett’s test are indicated as follows: *P < 0.05; **P < 0.01. V, vehicle, (a) Effects of quinpirole, (b) effects of 7-OH-DPAT, (c) effects of PD 128907, (d) effects of U-91356A.

Fig. 3

Effects of dopamine agonists on locomotor activity in dopaminergic (DA) D2R wild-type (WT) and knockout (KO) mice. Vertical axes: mean number of locomotor activity counts during a 60-min observation period. Horizontal axes: drug dose in mg/kg. Filled and open points represent activity counts for DA D2R WT and KO mice, respectively. Vertical bars indicate ± SEM. Each dose was examined in four to six mice. Statistical significance of results versus vehicle (V) according to a Dunnett’s test in WT mice are indicated as follows: *P < 0.05; **P < 0.01. No significant effects were observed in KO mice, (a) Effects of quinpirole, (b) effects of 7-OH-DPAT, (c) effects of PD 128907, (d) effects of U-91356A.

Fig. 4

Effects of dopamine agonists on locomotor activity in dopaminergic (DA) D3R wild-type (WT) and knockout (KO) mice.. Vertical axes: mean number of locomotor activity counts during a 60-min observation period. Abscissae: drug dose in mg/kg. Filled and open points represent activity counts for DA D3R WT and KO mice, respectively. Vertical bars indicate ± SEM. Each dose was examined in six mice. Statistical significance of results versus vehicle (V) according to a Dunnett’s test in WT or KO mice are indicated as follows: *P < 0.05; **P < 0.01. (a) Effects of quinpirole, (b) effects of 7-OH-DPAT, (c) effects of PD 128907, (d) effects of U-91356A.

Fig. 5

Effects of dopamine antagonists on locomotor activity in Swiss–Webster mice. Vertical axes: mean number of locomotor activity counts during a 60-min observation period. Horizontal axes: drug dose in mg/kg. Vertical bars indicate ± SEM. Each dose was examined in six to twelve mice. Statistical significance of results versus vehicle (V) according to a Dunnett’s test in wild-type mice are indicated as follows: *P < 0.05; **P < 0.01.

Fig. 6

Effects of combinations of quinpirole, 7-OH-DPAT, or PD 128907 with L-741626 on the locomotor activity of Swiss–Webster mice. Vertical axes: mean number of locomotor activity counts during a 60-min observation period. Horizontal axes: drug dose in mg/kg. Vertical bars indicate ± SEM. Each dose was examined in six to nine mice. Statistical significance versus vehicle and vehicle (V) group (according to the Dunnett’s test) are indicated as follows: *P < 0.05, **P < 0.01. Statistical significance of a given dose of agonist and vehicle versus that dose with a dose of antagonist according to the Dunnett’s test are indicated as followis: ^#P < 0.05, ^##P < 0.01. (a) Effects of quinpirole, (b) effects of 7-OH-DPAT, (c) effects of PD 128907.

Fig. 7

Effects of combinations of 1 mg/kg 7-OH-DPAT with either BP 897 or PG01037 on the locomotor activity of Swiss–Webster mice. Vertical axes: mean number of locomotor activity counts during a 60-min observation period. Horizontal axes: drug dose in mg/kg. Vertical bars indicate ± SEM. Each dose was examined in six to eight mice. Statistical significance according to the Fisher’s least significant difference test of 7-OH-DPAT with vehicle versus vehicle and vehicle results are as follows: *P < 0.05; **P < 0.001. Differences between agonist and vehicle versus agonist and antagonist were not statistically significant according to the Fisher’s least significant difference test (P ≥ 0.18).