The adenosine A2A antagonist KF17837 reverses the locomotor suppression and tremulous jaw movements induced by haloperidol in rats: possible relevance to parkinsonism

Recent evidence indicates that adenosine A2A receptors modulate the activity of striatal neurons, and that antagonists of this receptor may have actions in various animal models related to motor function. Four experiments were conducted to study the effects of systemic injections of the adenosine A2A antagonist KF17837 on the behavioral effects produced by repeated administration of the dopamine (DA) antagonist haloperidol. In the first two experiments, it was shown that repeated 0.5 mg/kg haloperidol severely suppressed open-field locomotor activity, and that KF17837 (0.0-20.0 mg/kg) did not significantly increase open-field locomotor activity. The third experiment demonstrated that injections of KF17837 (0.0-20.0 mg/kg) completely reversed the suppression of locomotion induced by haloperidol, and also increased rearing behavior in haloperidol-treated rats. Previous research has reported that haloperidol induces tremulous jaw movements that have many of the characteristics of parkinsonian tremor. The fourth experiment demonstrated that i.p. injections of KF17837 (0.0-20.0 mg/kg) also suppressed haloperidol-induced tremulous jaw movements. Taken together, the results of these experiments indicate that adenosine A2A antagonism can reverse the locomotor suppression and tremulous movements induced by DA antagonism. This profile of activity is consistent with the hypothesis that antagonism of adenosine A2A receptors can result in an antiparkinsonian effect in animal models. (C) 2003 Elsevier B.V. All rights reserved.