Opposing patterns of signaling activation in dopamine D1 and D2 receptor-expressing striatal neurons in response to cocaine and haloperidol. Export

@article{citeulike:3090817, abstract = {Psychostimulants and other drugs of abuse activate extracellular signal-regulated kinase (ERK) in the striatum, through combined stimulation of dopamine D(1) receptors (D1Rs) and glutamate NMDA receptors. Antipsychotic drugs activate similar signaling proteins in the striatum by blocking dopamine D(2) receptors (D2Rs). However, the neurons in which these pathways are activated by psychotropic drugs are not precisely identified. We used transgenic mice, in which enhanced green fluorescent protein (EGFP) expression was driven by D1R promoter (drd1a-EGFP) or D2R promoter (drd2-EGFP). We confirmed the expression of drd1a-EGFP in striatonigral and drd2-EGFP in striatopallidal neurons. Drd2-EGFP was also expressed in cholinergic interneurons, whereas no expression of either promoter was detected in GABAergic interneurons. Acute cocaine treatment increased phosphorylation of ERK and its direct or indirect nuclear targets, mitogen- and stress-activated kinase-1 (MSK1) and histone H3, exclusively in D1R-expressing output neurons in the dorsal striatum and nucleus accumbens. Cocaine-induced expression of c-Fos and Zif268 predominated in D1R-expressing neurons but was also observed in D2R-expressing neurons. One week after repeated cocaine administration, cocaine-induced signaling responses were decreased, with the exception of enhanced ERK phosphorylation in dorsal striatum. The responses remained confined to D1R neurons. In contrast, acute haloperidol injection activated phosphorylation of ERK, MSK1, and H3 only in D2R neurons and induced c-fos and zif268 predominantly in these neurons. Our results demonstrate that cocaine and haloperidol specifically activate signaling pathways in two completely segregated populations of striatal output neurons, providing direct evidence for the selective mechanisms by which these drugs exert their long-term effects.}, address = {Inserm UMR-S 839, Paris, France.}, author = {Bertran-Gonzalez, J. and Bosch, C. and Maroteaux, M. and Matamales, M. and Herv\'{e}, D. and Valjent, E. and Girault, J. A.}, citeulike-article-id = {3090817}, citeulike-linkout-0 = {http://dx.doi.org/10.1523/JNEUROSCI.1039-08.2008}, citeulike-linkout-1 = {http://www.jneurosci.org/cgi/content/abstract/28/22/5671}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18509028}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18509028}, day = {28}, doi = {10.1523/JNEUROSCI.1039-08.2008}, issn = {1529-2401}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, keywords = {d1, d1cre, d2}, month = {May}, number = {22}, pages = {5671--5685}, posted-at = {2009-03-09 11:47:01}, priority = {5}, title = {Opposing patterns of signaling activation in dopamine D1 and D2 receptor-expressing striatal neurons in response to cocaine and haloperidol.}, url = {http://dx.doi.org/10.1523/JNEUROSCI.1039-08.2008}, volume = {28}, year = {2008} }

TY - JOUR ID - citeulike:3090817 L3 - citeulike-article-id:3090817 N2 - Psychostimulants and other drugs of abuse activate extracellular signal-regulated kinase (ERK) in the striatum, through combined stimulation of dopamine D(1) receptors (D1Rs) and glutamate NMDA receptors. Antipsychotic drugs activate similar signaling proteins in the striatum by blocking dopamine D(2) receptors (D2Rs). However, the neurons in which these pathways are activated by psychotropic drugs are not precisely identified. We used transgenic mice, in which enhanced green fluorescent protein (EGFP) expression was driven by D1R promoter (drd1a-EGFP) or D2R promoter (drd2-EGFP). We confirmed the expression of drd1a-EGFP in striatonigral and drd2-EGFP in striatopallidal neurons. Drd2-EGFP was also expressed in cholinergic interneurons, whereas no expression of either promoter was detected in GABAergic interneurons. Acute cocaine treatment increased phosphorylation of ERK and its direct or indirect nuclear targets, mitogen- and stress-activated kinase-1 (MSK1) and histone H3, exclusively in D1R-expressing output neurons in the dorsal striatum and nucleus accumbens. Cocaine-induced expression of c-Fos and Zif268 predominated in D1R-expressing neurons but was also observed in D2R-expressing neurons. One week after repeated cocaine administration, cocaine-induced signaling responses were decreased, with the exception of enhanced ERK phosphorylation in dorsal striatum. The responses remained confined to D1R neurons. In contrast, acute haloperidol injection activated phosphorylation of ERK, MSK1, and H3 only in D2R neurons and induced c-fos and zif268 predominantly in these neurons. Our results demonstrate that cocaine and haloperidol specifically activate signaling pathways in two completely segregated populations of striatal output neurons, providing direct evidence for the selective mechanisms by which these drugs exert their long-term effects. IS - 22 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience SN - 1529-2401 AD - Inserm UMR-S 839, Paris, France. EP - 5685 TI - Opposing patterns of signaling activation in dopamine D1 and D2 receptor-expressing striatal neurons in response to cocaine and haloperidol. VL - 28 SP - 5671 KW - d1 KW - d1cre KW - d2 AU - Bertran-Gonzalez, J AU - Bosch, C AU - Maroteaux, M AU - Matamales, M AU - Hervé, D AU - Valjent, E AU - Girault, JA PY - 2008/05/28/ UR - http://dx.doi.org/10.1523/JNEUROSCI.1039-08.2008 ER -