Amphetamine-evoked gene expression in striatopallidal neurons: regulation by corticostriatal afferents and the ERK/MAPK signaling cascade
Version of Record online: 6 SEP 2004
Journal of Neurochemistry
Volume 91, Issue 2, pages 337–348, October 2004
How to Cite
Ferguson, S. M. and Robinson, T. E. (2004), Amphetamine-evoked gene expression in striatopallidal neurons: regulation by corticostriatal afferents and the ERK/MAPK signaling cascade. Journal of Neurochemistry, 91: 337–348. doi: 10.1111/j.1471-4159.2004.02712.x
- Issue online: 10 SEP 2004
- Version of Record online: 6 SEP 2004
- Received April 4, 2004; revised manuscript received June 14, 2004; accepted June 16, 2004.
- caudate nucleus;
- immediate early genes;
- in situ hybridization;
The environmental context in which psychostimulant drugs are experienced influences their ability to induce immediate early genes (IEGs) in the striatum. When given in the home cage amphetamine induces IEGs predominately in striatonigral neurons, but when given in a novel test environment amphetamine also induces IEGs in striatopallidal neurons. The source of the striatopetal projections that regulate the ability of amphetamine to differentially engage these two striatofugal circuits has never been described. We report that transection of corticostriatal afferents selectively blocks, whereas enhancement of cortical activity with an ampakine selectively augments, the number of amphetamine-evoked c-fos-positive striatopallidal (but not striatonigral) neurons. In addition, blockade of the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) signaling cascade preferentially inhibits the number of amphetamine-evoked c-fos-positive striatopallidal neurons. These results suggest that glutamate released from corticostriatal afferents modulates the ability of amphetamine to engage striatopallidal neurons through an ERK/MAPK signaling-dependent mechanism. We speculate that this may be one mechanism by which environmental context facilitates some forms of drug experience-dependent plasticity, such as psychomotor sensitization.