Delayed, context- and dopamine D1 receptor-dependent activation of ERK in morphine-sensitized mice.
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.
Borgkvist
Anders
A
Department of Neuroscience, Karolinska Institutet, 17177 Stockholm, Sweden. anders.borgkvist@ki.se
Valjent
Emmanuel
E
Santini
Emanuela
E
Hervé
Denis
D
Girault
Jean-Antoine
JA
Fisone
Gilberto
G
D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal / Q000187:drug effects; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000008:administration & dosage*; D009021:Morphine Dependence / Q000201:enzymology*; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000187:drug effects / Q000201:enzymology; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000235:genetics; D013997:Time Factors
D000701:Analgesics, Opioid; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D009020:Morphine; D048049:Extracellular Signal-Regulated MAP Kinases