The present address of C. Sanchis-Segura is the Area de Psicobiologia, Universitat Jaume I, Castello (12071), Spain.
Amphetamine regulates NR2B expression in Go2α knockout mice and thereby sustains behavioral sensitization
Article first published online: 23 JUL 2010
© 2010 The Authors. Journal Compilation © 2010 International Society for Neurochemistry
Journal of Neurochemistry
Volume 115, Issue 1, pages 234–246, October 2010
How to Cite
Brunk, I., Sanchis-Segura, C., Blex, C., Perreau-Lenz, S., Bilbao, A., Spanagel, R. and Ahnert-Hilger, G. (2010), Amphetamine regulates NR2B expression in Go2α knockout mice and thereby sustains behavioral sensitization. Journal of Neurochemistry, 115: 234–246. doi: 10.1111/j.1471-4159.2010.06921.x
- Issue published online: 15 SEP 2010
- Article first published online: 23 JUL 2010
- Received June 25, 2010; revised manuscript received July 13, 2010; accepted July 13, 2010.
- behavioral sensitization;
- D1/D2 receptor signaling;
- glutamate receptor;
J. Neurochem. (2010) 115, 234–246.
The α-subunit of Go2 is a regulator of dopamine (DA) homeostasis. Deletion of the protein results in an imbalance of the direct and indirect DA pathway by reducing D1 and increasing D2 receptors. As a result, cocaine-induced behavioral sensitization is abolished. Here we show that repeated amphetamine injections in Go2α−/− mice induced a similar D1/D2 receptor ratio shift as cocaine but surprisingly the knockouts developed normal behavioral sensitization. DA receptor signaling following either cocaine or amphetamine treatment was also similar in Go2α−/− mice suggesting another mechanism involved in the differential behavioral response. Evidence is increasing that DA–glutamate interactions in the striatum determine psychostimulant action. In this line, repeated amphetamine injections led to a twofold increase in the amount of the NMDA receptor subunit NR2B in Go2α−/− mice resulting in an enhanced inhibition of the indirect DA pathway. This effect is not seen after cocaine treatment. Furthermore, amphetamine but not cocaine treatment maintained the ratio between the glutamate receptor mGluR1/5 interacting proteins Homer and Homer1a in the knockouts thereby sustaining the direct pathway. We conclude that amphetamine provokes behavioral sensitization in Go2α−/− mice by an enhanced inhibition of the indirect pathway without disturbing the direct pathway thereby overcoming the imbalance in the DArgic system.