title: 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.
authors.affiliation: Department of Biochemistry, Laboratory of Studies on the Purinergic System, Graduation Program in Biological Sciences-Biochemistry, Federal University of Rio Grande do Sul, Health and Basic Sciences Institute, Bairro Santana, Brazil.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Mioranzza
authors.forename: Paulo Henrique S
authors.initials: PH
authors.lastname: Botton
authors.forename: Marcelo S
authors.initials: MS
authors.lastname: Costa
authors.forename: Janaina
authors.initials: J
authors.lastname: Espinosa
authors.forename: Vanessa
authors.initials: V
authors.lastname: Kazlauckas
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Ardais
authors.forename: Diogo O
authors.initials: DO
authors.lastname: Souza
authors.forename: Lisiane O
authors.initials: LO
authors.lastname: Porciúncula
mesh_terms: D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism; D015153:Blotting, Western; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D005625:Frontal Lobe / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D000697:Central Nervous System Stimulants; D043682:Receptor, Adenosine A1; D014970:Xanthines; D008774:Methylphenidate; C051360:1,3-dipropyl-8-cyclopentylxanthine