Blockade of adenosine A(1) receptors prevents methylphenidate-induced impairment of object recognition task in adult mice |
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Authors: | Mioranzza Sabrina Costa Marcelo S Botton Paulo Henrique S Ardais Ana Paula Matte Vanessa Lague Espinosa Janaina Souza Diogo O Porciúncula Lisiane O |
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Institution: | a Federal University of Rio Grande do Sul, Health and Basic Sciences Institute, Department of Biochemistry, Graduation Program in Biological Sciences — Biochemistry, Laboratory of Studies on the Purinergic System, Porto Alegre/RS, Brazil 90035-003b Graduation Program in Biological Sciences — Neurosciences, Porto Alegre/RS, Brazil 90035-003 |
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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 (15 days) administration of methylphenidate (5 mg/kg, i.p.), or an acute overdosage (50 mg/kg, i.p) in order to model misuse. Memory was assessed in the inhibitory avoidance and object recognition task. Acute administration 5 mg/kg improved whereas 50 mg/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 1 mg/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. |
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Keywords: | ADHD Attention-deficit/hyperactivity disorder DMSO dimethyl sulfoxide DPCPX 8-cyclopentyl-1 3-dipropylxanthine MPH Methylphenidate SHR Spontaneously hypertensive rats VMAT2 Vesicular monoamine transporter 2 |
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