Yawning and hypothermia in rats: effects of dopamine D3 and D2 agonists and antagonists.
BACKGROUND
Identification of behaviors specifically mediated by the dopamine D2 and D3 receptors would allow for the determination of in vivo receptor selectivity and aide the development of novel therapeutics for dopamine-related diseases.


OBJECTIVE
These studies were aimed at evaluating the specific receptors involved in the mediation of D2/D3 agonist-induced yawning and hypothermia.


METHODS
The relative potencies of a series of D2-like agonists to produce yawning and hypothermia were determined. The ability of D3-selective and D2-selective antagonists to inhibit the induction of yawning and hypothermia were assessed and a series of D2/D3 antagonists were characterized with respect to their ability to alter yawning induced by a low and high dose of PD-128,907 and sumanirole-induced hypothermia.


RESULTS
D3-preferring agonists induced yawning at lower doses than those required to induce hypothermia and the D2-preferring agonist, sumanirole, induced hypothermia at lower doses than were necessary to induce yawning. The rank order of D3 selectivity was pramipexole > PD-128,907 = 7-OH-DPAT = quinpirole = quinelorane > apomorphine = U91,356A. Sumanirole had only D2 agonist effects. PG01,037, SB-277,011A, and U99,194 were all D3-selective antagonists, whereas haloperidol and L-741,626 were D2-selective antagonists and nafadotride's profile of action was more similar to the D2 antagonists than to the D3 antagonists.


CONCLUSIONS
D3 and D2 receptors have specific roles in the mediation of yawning and hypothermia, respectively, and the analysis of these effects allow inferences to be made regarding the selectivity of D2/D3 agonists and antagonists with respect to their actions at D2 and D3 receptors.
Collins
Gregory T
GT
Department of Pharmacology, University of Michigan Medical School, 1301 MSRB III, 1150 W. Medical Center Drive, Ann Arbor, MI 48109-0632, USA.
Newman
Amy Hauck
AH
Grundt
Peter
P
Rice
Kenner C
KC
Husbands
Stephen M
SM
Chauvignac
Cédric
C
Chen
Jianyong
J
Wang
Shaomeng
S
Woods
James H
JH
D000704:Analysis of Variance; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D007035:Hypothermia / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D050637:Receptors, Dopamine D3 / Q000819:agonists* / Q000037:antagonists & inhibitors*; D015000:Yawning / Q000187:drug effects*
D065127:Dopamine D2 Receptor Antagonists; C493595:Drd3 protein, rat; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3