Cross-sensitization between the motor activating effects of bromocriptine and caffeine: role of adenosine A2A receptors

The acute motor response to caffeine was studied in rats repeatedly treated with vehicle or the dopamine D2 agonist bromocriptine either in a novel cage or in the home cage. Rats receiving bromocriptine (5 mg/kg i.p.) in a novel cage were sensitized to the motor stimulating effects of bromocriptine itself and showed cross-sensitization to the acute administration of low (10 mg/kg s.c.) but not high (25 mg/kg s.c.) doses of caffeine, no matter if the novel cage was identical or different from the test cage. In contrast, caffeine (10 mg/kg i.p.) administered to rats which had received bromocriptine (5 mg/kg i.p.) in the home cage and which showed no sign of a sensitized response to bromocriptine, failed to show an increased locomotor and stereotyped response as compared to vehicle pretreated rats. Similarly to caffeine, the selective adenosine A2A antagonist SCH 58261 (3 mg/kg i.p.) showed an increased motor response in bromocriptine sensitized rats. The sensitized response to caffeine or SCH 58261 did not appear to be due to an higher basal motor activity of bromocriptine sensitized rats since acute administration of vehicle induced a similar motor response in bromocriptine and vehicle pretreated rats. Dopamine D2 and adenosine A2A receptors are colocalized in striatal efferent neurons where they control in an opposite direction motor behavior. The results of the present study showed that changes in the sensitivity of D2 receptors influenced the sensitivity of the adenosine antagonist caffeine through an action on A2A receptors. D2 and A2A receptors, therefore, not only acutely interact in the mediation of motor behavior but long-term modification of the D2 receptors, such as sensitization, affected the response of adenosine A2A receptors