The thyrotrophin-releasing hormone analogue MK771 induces tic-like behaviours: the effects of dopamine D 1 and D 2 receptor antagonists

Abstract

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 D 1 and D 2 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 D 1 receptor antagonists (+)-7-chloro-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro(1 H)-3-benzazepine 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 D 2 receptor antagonists raclopride (3.0 and 5.0 mg/kg) and sulpiride (5.0 and 10.0 mg/kg). D 1 but not D 2 receptor antagonists attenuated MK771-induced forepaw licking. MK771-induced blinking, therefore, appears not to involve dopamine D 1 or D 2 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 D 1 but not D 2 receptors.