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.

Methylphenidate Causes Behavioral Impairments and Neuron and Astrocyte Loss in the Hippocampus of Juvenile Rats

“…On the other hand, acute treatment in adult mice of 5 mg/kg of MPH improved, while the dose 50 mg/kg worsened object recognition memory and aversive memory [67]. Both dosing regimens did not change locomotor activity of animals and increased the number of entries and the time spent in open arms [68]. Our results suggest that rats chronically treated with MPH have less interest in exploring new environments and objects and thus the problems observed in memory could be explained, at least in part by acquisition deficits.…”

Heritable Differences in Catecholamine Signaling Modulate Susceptibility to Trauma and Response to Methylphenidate Treatment: Relevance for PTSD

“…We also investigated the effects of chronic treatment with methylphenidate in the predator stress model of PTSD in males and asked if COMTval158met modulated treatment response. Acute low doses of methylphenidate (<5 mg/kg) reduce anxiety-like behaviors (Koike et al, 2009; Mioranzza et al, 2010), whereas high doses (>7 mg/kg) have anxiogenic effects (Ihne et al, 2012). We chose a dose of MPD that selectively increases catecholamine release in cortex while having little effect in striatum in mice, to specifically target circuits that are most sensitive to COMT variation (Chen et al, 2004; Tunbridge, 2010; Risbrough et al, 2014).…”

Repetitive systemic morphine alters activity‐dependent plasticity of schaffer–collateral–CA1 pyramidal cell synapses: Involvement of adenosine A1 receptors and adenosine deaminase

“…To ensure equal protein loading and accurate change of protein abundance, membranes with Ponceau S were scanned, and densitometric values were measured at 37 kDa (for A1R) and at 41 kDa (for ADA). The values were used to obtain adenosine A1R or ADA density/Ponceau S density ratio (Mioranzza et al, ).…”