The clonidine-induced self-injurious behavior of mice involves purinergic mechanisms.

Mode of action of clonidine involved in self-injurious behavior was assessed in mice. Single injection of clonidine (50 mg/kg, IP) evoked a self-biting which occurred more frequently under the condition of isolation and food-deprivation for 24 hr. The clonidine-induced self-biting was not reduced, but rather potentiated by pretreatment with phentolamine (10 mg/kg). This behavior was enhanced by theophylline (20 mg/kg) but was inhibited to some extent by adenosine (10 mg/kg) or dipyridamole (10 mg/kg). In addition, the self-injurious behavior was completely antagonized by combined pretreatment with adenosine (10 mg/kg) and dipyridamole (10 mg/kg), and by potent adenosine agonists, such as N6-(L-phenylisopropyl) adenosine (0.2 mg/kg) and N6-cyclohexyladenosine (0.2 mg/kg). These results, therefore, suggest that the clonidine-induced self-biting could be substantially attributed to adenosine A1-receptor blockade as documented for pharmacological property of theophylline in the brain.