The thyrotrophin-releasing hormone analogue MK771 induces tic-like behaviours: the effects of dopamine D1 and D2 receptor antagonists.
Thyrotrophin-releasing hormone (TRH) and its analogues induce tic-like behaviours in rodents such as blinking and forepaw licking. Changes in spontaneous blinking frequency are observed in several disease states with dopamine abnormalities and dopaminergic agents modulate blinking. We have therefore investigated the effects of dopamine D1 and D2 receptor antagonists on TRH analogue (1-pyro-2-aminoadipyl-L-histidyl-L-thiazolidine-4-carboxamide; MK771)-induced blinking and bouts of forepaw licking. MK771 (2.5 mg/kg)-induced blinking was not attenuated by the dopamine D1 receptor antagonists (+)-7-chloro-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro(1H)-3-benzazep ine maleate (SCH23390) (0.01, 1.0 and 5.0 mg/kg) and ((-)-trans-6,7,7a,8,9,13b-hexahydro-3-chloro-2-hydroxy-N-methyl-5- H-benz[2,1b]azepine (SCH39166; 1.0 and 5.0 mg/kg) or the dopamine D2 receptor antagonists raclopride (3.0 and 5.0 mg/kg) and sulpiride (5.0 and 10.0 mg/kg). D1 but not D2 receptor antagonists attenuated MK771-induced forepaw licking. MK771-induced blinking, therefore, appears not to involve dopamine D1 or D2 receptors and contrary to previously held belief dopamine does not appear to be pivotal in the control of blinking, while MK771-induced forepaw licking is modulated by dopamine D1 but not D2 receptors.
McCreary
A C
AC
School of Life and Health Sciences, Aston University, Birmingham, UK.
Handley
S L
SL
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001526:Behavioral Symptoms / Q000139:chemically induced / Q000517:prevention & control; D001552:Benzazepines / Q000494:pharmacology; D001767:Blinking / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D020891:Raclopride; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D012457:Salicylamides / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology; D053778:Thiazolidines; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013981:Tic Disorders / Q000139:chemically induced / Q000517:prevention & control*
D000928:Antidepressive Agents; D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017447:Receptors, Dopamine D1; D012457:Salicylamides; D053778:Thiazolidines; C058081:ecopipam; D020891:Raclopride; D013973:Thyrotropin-Releasing Hormone; C021597:pyro(l-alpha-aminoadipyl)-L-histidyl-L-thiazolidine-4-carboxamide; D013469:Sulpiride