Blockade of adenosine A(1) receptors prevents methylphenidate-induced impairment of object recognition task in adult mice.
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 A(1) receptors in the frontal cortex, but this receptor was not involved in its anxiolytic effects. In this study, the role of adenosine A(1) 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 (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 A(1) receptors immunocontent in the frontal cortex. The selective adenosine A(1) 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 A(1) receptors may play a role in the methylphenidate actions probably by interfering with dopamine-enhancing properties of this drug.
Department of Biochemistry, Laboratory of Studies on the Purinergic System, Federal University of Rio Grande do Sul, Health and Basic Sciences Institute, Porto Alegre/RS, Brazil.
Sabrina
S
Mioranzza
Marcelo S
MS
Costa
Paulo Henrique S
PH
Botton
Ana Paula
AP
Ardais
Vanessa Lague
VL
Matte
Janaina
J
Espinosa
Diogo O
DO
Souza
Lisiane O
LO
Porciúncula
D058916:Adenosine A1 Receptor Antagonists / Q000008:administration & dosage; D000704:Analysis of Variance; D000818:Animals; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004924:Escape Reaction / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007266:Inhibition, Psychological; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D008774:Methylphenidate / Q000633:toxicity*; D051379:Mice; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D021641:Recognition, Psychology / Q000187:drug effects* / Q000502:physiology; D014970:Xanthines / Q000008:administration & dosage
D058916:Adenosine A1 Receptor Antagonists; D000697:Central Nervous System Stimulants; D043682:Receptor, Adenosine A1; D014970:Xanthines; D008774:Methylphenidate; C051360:1,3-dipropyl-8-cyclopentylxanthine