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Publication : Delayed, context- and dopamine D1 receptor-dependent activation of ERK in morphine-sensitized mice.

First Author  Borgkvist A Year  2008
Journal  Neuropharmacology Volume  55
Issue  2 Pages  230-7
PubMed ID  18614186 Mgi Jnum  J:252964
Mgi Id  MGI:6100646 Doi  10.1016/j.neuropharm.2008.05.028
Citation  Borgkvist A, et al. (2008) Delayed, context- and dopamine D1 receptor-dependent activation of ERK in morphine-sensitized mice. Neuropharmacology 55(2):230-7
abstractText  Exposure to cues previously associated with intake of substances of abuse can promote drug related responses. In this study, we have examined the effect of exposure to a drug-associated context on the expression of morphine psychomotor sensitization. We show that sensitization is markedly increased in mice examined 4 weeks after the last morphine injection. In addition, this incubation period confers to the environment paired with morphine the ability to increase ERK phosphorylation in the shell (but not the core) of the nucleus accumbens. Using transgenic mice with enhanced green fluorescent protein (EGFP) expression under the control of the dopamine D1 receptor (D1R) (Drd1a-EGFP) or D2 receptor promoter (Drd2-EGFP) we show that context-dependent ERK phosphorylation is restricted to D1R-expressing medium spiny neurons. Furthermore, this effect depends on D1R activation. These data show that, following repeated morphine injections, a drug-free period induces context-dependent phosphorylation of ERK in a specific population of neurons within the nucleus accumbens shell. This activation is associated to enhanced psychomotor sensitization and may be implicated in context-elicited drug seeking induced by repeated exposure to drugs of abuse.
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