A crucial role for forebrain adenosine A2A receptors in amphetamine sensitization

Elena Bastia, Yue Hang Xu, Angela C. Scibelli, Yuan Ji Day, Joel Linden, Jiang Fan Chen, Michael A. Schwarzschild*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

88 引文 斯高帕斯(Scopus)

摘要

Adenosine A2A receptors (A2ARs) are well positioned to influence the maladaptive CNS responses to repeated dopaminergic stimulation in psychostimulant addiction. Expression of A2ARs in brain is largely restricted to the nucleus accumbens and striatum, where molecular adaptations mediate chronic effects of psychostimulants such as behavioral sensitization. Using a novel forebrain-specific conditional (Cre/loxP system) knockout of the A2AR in coordination with classical pharmacological approaches, we investigated the involvement of brain A2ARs in amphetamine-induced behavioral sensitization. Tissue-specific, functional disruption of the receptor was confirmed by autoradiography, PCR1 and the loss of A 2A antagonist-induced motor stimulation. Daily treatment with amphetamine for 1 week markedly enhanced locomotor responses on day 8 in control mice and the sensitization remained robust after a week of washout. Their conditional knockout littermates however showed no sensitization to amphetamine on day 8 and only a modest sensitization following the washout. Pharmacological blockade of adenosine A2ARs also was able to block the development (but not the expression) of sensitization in multiple mouse strains. Thus activation of brain A2ARs plays a critical role in developing augmented psychomotor responses to repeated psychostimulant exposure.

原文英語
頁(從 - 到)891-900
頁數10
期刊Neuropsychopharmacology
30
發行號5
DOIs
出版狀態已出版 - 05 2005
對外發佈

指紋

深入研究「A crucial role for forebrain adenosine A2A receptors in amphetamine sensitization」主題。共同形成了獨特的指紋。

引用此