title: Chronic treatment with DCPCX, an adenosine A(1) antagonist, worsens long-term memory.
abstract: Alzheimer's disease is characterized by progressive cognitive disturbances and neurotransmitter dysfunction. Previous studies targeting the adrenergic A1 pathway suggest that this plays a role in cognitive impairment in Alzheimer's disease. Previous studies have reported that acute treatment with A1 antagonists appears to improve behavioral deficits in rodent models of memory and behavioral impairment. In this study, we addressed whether the chronic administration of 8-cyclopentyl-1,3-dipropylxanthine, a potent and selective adenosine A1 antagonist, could reverse the memory deficits found in aged APPswe/PS1dE9 mice. Chronic treatment did not improve memory in the APPswe/PS1dE9 mouse model and resulted in reduced exploratory behavior, suggestive of reduced anxiety, and a worsening of long-term memory in nontransgenic mice. These results have important implications for understanding the mechanisms of A1 receptor modulation as a target in Alzheimer's disease therapy.
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, TX 77204, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Vollert
authors.forename: Gloria S
authors.initials: GS
authors.lastname: Forkuo
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bond
authors.forename: Jason L
authors.initials: JL
authors.lastname: Eriksen
mesh_terms: D058916:Adenosine A1 Receptor Antagonists / Q000008:administration & dosage*; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D000818:Animals; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology*; D057567:Memory, Long-Term / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016896:Treatment Outcome; D014970:Xanthines / Q000008:administration & dosage*
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine
keywords: Adenosine A(1) antagonist; Alzheimer's disease; Anxiolytic; Chronic treatment; Impaired learning