Blockade of adenosine A1 receptors prevents methylphenidate-induced impairment of object recognition task in adult mice

Abstract

Methylphenidate (MPH) is the preferred treatment used for attention-deficit/hyperactivity disorder (ADHD). Recently, misuse for MPH due to its apparent cognitive enhancer properties has been reported. Adenosine is a neuromodulator known to exert influence on the dopaminergic neurotransmission, which is the main pharmacological target of MPH. We have reported that an overdosage of MPH up-regulates adenosine A1 receptors in the frontal cortex, but this receptor was not involved in its anxiolytic effects. In this study, the role of adenosine A1 receptor was investigated on MPH-induced effects on aversive and recognition memory in adult mice. Adult mice received acute and chronic (15days) administration of methylphenidate (5mg/kg, i.p.), or an acute overdosage (50mg/kg, i.p) in order to model misuse. Memory was assessed in the inhibitory avoidance and object recognition task. Acute administration 5mg/kg improved whereas 50mg/kg disrupted recognition memory and decreased performance in the inhibitory avoidance task. Chronic administration did not cause any effect on memory, but decreased adenosine A1 receptors immunocontent in the frontal cortex. The selective adenosine A1 receptor antagonist, (DPCPX 1mg/kg, i.p.), prevented methylphenidate-triggered recognition memory impairment. Our findings showed that recognition memory rather than aversive memory was differently affected by acute administration at both doses. Memory recognition was fully impaired by the overdosage, suggesting that misuse can be harmful for cognitive functions. The adenosinergic system via A1 receptors may play a role in the methylphenidate actions probably by interfering with dopamine-enhancing properties of this drug.