Inhibitory effects of carbamazepine on clonidine-induced aggressive behavior in mice

A behavioral study was made of the effect of carbamazepine (CBZ) on aggressive behavior evoked by high dose of clonidine in mice. This aggressive behavior has been reported to involve blockade of central adenosine receptors with which CBZ has been suggested to interact. After a single injection of clonidine (50 mg/kg i.p.), aggressive responses such as attacking and biting began within 5-10 min, were most marked at 20 min and usually ceased within 60 min. This behavior was attenuated by CBZ (45 mg/kg i.p.) but potentiated by caffeine (20 mg/kg i.p.). In addition, it was markedly inhibited by haloperidol (1.0 mg/kg i.p.), but unaffected by prazosin (1.5 mg/kg i.p.) and yohimbine (1.0 mg/kg i.p.). The inhibitory effect of CBZ on the aggressive behavior was dose-dependent at doses ranging from 15 to 60 mg/kg, while a high dose of CBZ alone induced sedation. The stimulatory effect of caffeine on the aggressive behavior was antagonized by pretreatment with CBZ (50 mg/kg i.p.). These results suggest that the receptor involved in clonidine-induced aggressive behavior was not mediated through the alpha-2 adrenoreceptor, but rather the adenosine receptor, and that the effect of carbamazepine on the adenosine receptor was agonistic in contrast with the effect of caffeine (an adenosine antagonist).