The roles of calcium/calmodulin-dependent and Ras/mitogen-activated protein kinases in the development of psychostimulant-induced behavioral sensitization
Article first published online: 6 MAR 2003
Journal of Neurochemistry
Volume 85, Issue 1, pages 14–22, April 2003
How to Cite
Licata, S. C. and Pierce, R. C. (2003), The roles of calcium/calmodulin-dependent and Ras/mitogen-activated protein kinases in the development of psychostimulant-induced behavioral sensitization. Journal of Neurochemistry, 85: 14–22. doi: 10.1046/j.1471-4159.2003.01662.x
- Issue published online: 6 MAR 2003
- Article first published online: 6 MAR 2003
- Received August 2, 2002; revised manuscript received November 19, 2002; accepted December 17, 2002.
- L-type calcium channels;
- nucleus accumbens;
- ventral tegmental area
Although the development of behavioral sensitization to psychostimulants such as cocaine and amphetamine is confined mainly to one nucleus in the brain, the ventral tegmental area (VTA), this process is nonetheless complex, involving a complicated interplay between neurotransmitters, neuropeptides and trophic factors. In the present review we present the hypothesis that calcium-stimulated second messengers, including the calcium/calmodulin-dependent protein kinases and the Ras/mitogen-activated protein kinases, represent the major biochemical pathways whereby converging extracellular signals are integrated and amplified, resulting in the biochemical and molecular changes in dopaminergic neurons in the VTA that represent the critical neuronal correlates of the development of behavioral sensitization to psychostimulants. Moreover, given the important role of calcium-stimulated second messengers in the expression of behavioral sensitization, these signal transduction systems may represent the biochemical substrate through which the transient neurochemical changes associated with the development of behavioral sensitization are translated into the persistent neurochemical, biochemical and molecular alterations in neuronal function that underlie the long-term expression of psychostimulant-induced behavioral sensitization.