adenosine receptor antagonists do not disrupt rodent prepulse inhibition an improved side effect profile in the treatment of parkinsons disease腺苷受体拮抗剂不破坏啮齿动物前脉冲抑制一种改进的副作用的治疗帕金森病.pdfVIP

Hindawi Publishing Corporation Parkinson’s Disease Volume 2012, Article ID 591094, 9 pages doi:10.1155/2012/591094 Research Article Adenosine A2A Receptor Antagonists Do Not Disrupt Rodent Prepulse Inhibition: An Improved Side Effect Profile in the Treatment of Parkinson’s Disease Carina J. Bleickardt, Abigail L. LaShomb, Carrie E. Merkel, and Robert A. Hodgson Department of In Vivo Pharmacology, Neuroscience, Merck Research Laboratories, 2015 Galloping Hill Road, K-15-1600, Kenilworth, NJ 07033, USA Correspondence should be addressed to Carina J. Bleickardt, carina.bleickardt@ Received 29 July 2011; Accepted 9 September 2011 Academic Editor: Antonio Lucio Teixeira Copyright © 2012 Carina J. Bleickardt et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Parkinson’s disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra. Current treatments for PD focus on dopaminergic therapies, including L-dopa and dopamine receptor agonists. However, these treatments induce neuropsychiatric side effects. Psychosis, characterized by delusions and hallucinations, is one of the most serious such side effects. Adenosine A2A re- ceptor antagonism is a nondopaminergic treatment for PD with clinical and preclinical efficacy. The present studies assessed A2A antagonists SCH 412348 and istradefylline in rodent prepulse inhibition (PPI), a model of psychosis. Dopamine receptor agonists pramipexole (0.3–3 mg/kg), pergolide (0.3–3 mg/kg), and apomorphine (0.3–3 mg/kg) significantly disrupted PPI; ropinirole (1– 30 mg/kg) had no effect; L-dopa (100–300 mg/kg) disrupted rat but not mouse PPI. SCH 412348 (0.3–