Negative cross-talk between cocaine and the D₂ receptor agonist quinpirole on ERK 1/2 phosphorylation in mice striatum.

<p>In (<b>a</b>) WT (black bars) and σ₁ receptor KO (white bars) mouse striatal slices were treated with 1 µM quinpirole for 10 min, with 150 µM cocaine for 30 min or with cocaine for 30 min and, during the last 10 min, with quinpirole. Immunoreactive bands from six slices obtained from five WT or five KO animals were quantified for each condition. Values represent mean ± SEM of percentage of phosphorylation relative to basal levels found in untreated slices. No significant differences were obtained between the basal levels of the WT and the σ₁ receptor KO mice. Bifactorial ANOVA showed a significant (*p<0.05, **p<0.01, ***p<0.005) effect over basal. One-way ANOVA followed by Bonferroni post hoc tests showed a significant cocaine-mediated counteraction of quinpirole (^&p<0.05, ^&&p<0.01). In (<b>b</b>) a representative scheme summarizing the overall results is shown. Top images represent D₂ and D₁ receptors signaling in the indirect and direct striatal pathway neurons after dopamine binding. Bottom images represent the effect of cocaine increasing the dopamine by inhibiting dopamine transporters (DAT) and interacting with σ₁ receptors within σ₁-D₂ and σ₁-D₁ receptor heteromers, changing the dopamine receptor signaling.