Anxiolytic effect of carbamazepine in the elevated plus-maze: possible role of adenosine.

In order to extend previously reported observations with other animal models of anxiety, the effect of carbamazepine (CBZ) was presently measured in rats placed on the elevated plus-maze. Intraperitoneal injection of CBZ (5-40 mg/kg) increased the percentage of open arm entries as well as the percentage of time spent on the open arms of the maze, without affecting the total number of arm entries. This effect is characteristic of anxiolytic drugs. The inhibitor of adenosine neuronal uptake papaverine (5-40 mg/kg) caused a similar anxiolytic effect, whereas the adenosine receptor antagonist aminophylline (1-4 mg/kg) selectively decreased the percentage of open arm entries, indicative of an anxiogenic effect. Furthermore, the combination of an anxiogenic dose (4 mg/kg) of aminophylline with an anxiolytic dose (40 mg/kg) of CBZ resulted in cancellation of each other effects. Since reported neurochemical evidence shows that CBZ interacts with adenosine receptors, the present results provide preliminary support for a participation of this neurotransmitter in the anxiolytic action of CBZ.