Dopamine agonist-induced yawning in rats: A dopamine D3 receptor-mediated behavior

A specific role for the dopamine D3 receptor in behavior has yet to be elucidated. We now report that dopamine D2/D3 agonists elicit dose-dependent yawning behavior in rats, resulting in an inverted U-shaped dose-response curve. A series of experiments was directed toward the hypothesis that the induction of yawning is a D3 receptor-mediated effect, whereas the inhibition of the yawning observed at higher doses is due to competing D2 receptor activity. We compared several dopaminergic agonists with a range of in vitro D3 selectivity, including PD-128,907 [(S)-(+)-(4aR, 10bR)-3,4,4a, 10b-tetrahydro-4-propyl-2H,5H-[1] benzopyrano-[4,3-b]-1,4-oxazin-9-ol HCl], PD-128,908 [(R)-(-)-(4aS, 10bS)-3,4,4a, 10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin-9-ol HCl], quinelorane [(5aR-trans)-5,5a, 6,7,8, 9,9a, 10-octahydro-6-propylpyrido[2,3-g] quinazolin-2-amine dihydrochloride], pramipexole (N'-propyl-4,5,6,7-tetrahydrobenzothiazole-2,6-diamine), 7-OH-DPAT [(+/-)-7-hydroxy-2-dipropylaminotetralin HBr], quinpirole [trans-(-)-(4aR)-4,4a,5,6,7,8, 8a,9-octahydro-5-propyl-1H-pyrazolo[3,4-g] quinoline HCl], bromocriptine [(+)-2-bromo-12'- hydroxy-2'-(1-methylethyl)-5'-(2-methylpropyl) ergotaman-3',6'-18-trione methanesulfonate], and apomorphine [(R)-(-)-5,6,6a,7-tetrahydro-6-methyl-4H-dibenzo[de,g]quinoline-10,11-diol HCl] with respect to their ability to induce yawning in rats. A series of D2/D3 antagonists differing in selectivity for D3 over D2 receptors were evaluated for their ability to alter the effects of the dopamine agonists. The antagonists L-741,626 (3-[4-(4-chlorophenyl)-4-hydroxypiperidin-L-yl]methyl-1H-indole), haloperidol (4-[4-(4- chlorophenyl)-4- hydroxy.