Adenosine A1 receptors are modified by acute treatment with methylphenidate in adult mice

Abstract

In recent years misuse of methylphenidate (MPH) has been reported. The main pharmacological target of methylphenidate is the dopaminergic system. Adenosine is a neuromodulator that influences the dopaminergic neurotransmission, but studies on MPH and adenosine are still lacking. In this study, adult mice were acutely treated with MPH (5mg/kg, i.p.) and to model misuse, they received an acute overdosage (50mg/kg, i.p). The involvement of adenosine A(1) receptors in anxiety-related behavior and locomotor and exploratory activity was examined. The administration of methylphenidate (5 and 50mg/kg) 30 min before the exposure to open field arena did not modify locomotor activity. The anxiolytic-like behavior was observed with both doses of MPH as revealed by the increase on the number of entries and the time spent in the open arms in the elevated plus-maze. Pre treatment with selective adenosine A(1) receptor antagonist (DPCPX 1mg/kg, i.p.) did not prevent anxiolytic effect caused by MPH 50mg/kg. Immunoblotting of frontal cortex and hippocampal extracts revealed that MPH 50mg/kg increased 88% adenosine A(1) receptor density in the frontal cortex. Extracts from hippocampus did not reveal any differences in the adenosine A(1) receptor density. Our findings ruled out the participation of adenosine A(1) receptors on the MPH-triggered anxiolytic effects. However, the density of adenosine A(1) receptors increased in a brain area strictly involved in the MPH-mediated effects. Thus, the adenosinergic system may play a role in the methylphenidate actions in the central nervous system.