| Autor: |
Bastia, Elena, Yue-Hang Xu, Scibelli, Angela C., Yuan-Ji Day, Joel Linden, Jiang-Fan Chen, Schwarzschild, Michael A. |
| Předmět: |
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| Zdroj: |
Neuropsychopharmacology; May2005, Vol. 30 Issue 5, p891-900, 10p, 1 Diagram, 16 Graphs |
| Abstrakt: |
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/IoxP 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, PCR, and the loss of A2A antagonist-induced motor stimulation. Daily treatment with amphetamine for I week markedly enhanced locomotor responses on day 8 in control mice and the sensitization remained robust after a week of washout. Their conditional knockout Iittermates however showed no sensitization to amphetamine on day 8 and only a modest sensitization following the washout. Pharmacolosical 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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