title: Adenosine receptor antagonists improve short-term object-recognition ability of spontaneously hypertensive rats: a rodent model of attention-deficit hyperactivity disorder.
abstract: The strain of spontaneously hypertensive rats (SHR) is considered a genetic model for the study of attention-deficit hyperactivity disorder (ADHD), as it displays hyperactivity, impulsivity and poorly sustained attention. Recently, we have shown the involvement of adenosinergic neuromodulation in the SHR's short-term and long-term memory impairments. In this study, we investigated the performance of male and female SHR in a modified version of the object-recognition task (using objects with different structural complexity) and compared them with Wistar rats, a widely used outbred rat strain for the investigation of learning processes. The suitability of the SHR strain to represent an animal model of ADHD, as far as mnemonic deficits are concerned, was pharmacologically validated by the administration of methylphenidate, the first-choice drug for the treatment of ADHD patients. The role of adenosine A1 and A2A receptors in object discrimination was investigated by the administration of caffeine (nonselective antagonist) or selective adenosine receptor antagonists. Wistar rats discriminated all the objects used (cube vs. pyramid; cube vs. T-shaped object), whereas SHR only discriminated the most structurally distinct pairs of objects (cube vs. pyramid). Pretraining administration of methylphenidate [2 mg/kg, intraperitoneal (i.p.)], caffeine (1-10 mg/kg, i.p.), the selective adenosine receptor antagonists DPCPX (8-cyclopenthyl-1,3-dipropylxanthine; A1 antagonist, 5 mg/kg, i.p.) and ZM241385 (A2A antagonist, 1.0 mg/kg, i.p.), or the association of ineffective doses of DPCPX (3 mg/kg) and ZM241385 (0.5 mg/kg), improved the performance of SHR in the object-recognition task. These findings show that the discriminative learning impairments of SHR can be attenuated by the blockade of either A1 or A2A adenosine receptors, suggesting that adenosinergic antagonists might represent potentially interesting drugs for the treatment of ADHD.
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil.
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: Pires
authors.forename: Fabrício A
authors.initials: FA
authors.lastname: Pamplona
authors.forename: Pablo
authors.initials: P
authors.lastname: Pandolfo
authors.forename: Daniel
authors.initials: D
authors.lastname: Fernandes
authors.forename: Rui D S
authors.initials: RD
authors.lastname: Prediger
authors.forename: Reinaldo N
authors.initials: RN
authors.lastname: Takahashi
mesh_terms: D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D001794:Blood Pressure / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D008570:Memory, Short-Term / Q000187:drug effects* / Q000502:physiology; D008774:Methylphenidate / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000502:physiology; D043683:Receptors, Adenosine A2 / Q000502:physiology; D021641:Recognition, Psychology / Q000187:drug effects* / Q000502:physiology; D014227:Triazines / Q000008:administration & dosage / Q000494:pharmacology; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology; D014970:Xanthines / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D043682:Receptor, Adenosine A1; D043683:Receptors, Adenosine A2; D014227:Triazines; D014230:Triazoles; D014970:Xanthines; C097270:ZM 241385; D008774:Methylphenidate; D002110:Caffeine; C051360:1,3-dipropyl-8-cyclopentylxanthine