Effect of Dopamine D1 Receptor Activation on Extinction of Morphine CPP

Abstract

The dopamine D1 receptor (D1R) mediates drug reward and morphology of accumbal neurons. We used a morphine conditioned place preference (CPP) mouse model to study the role of D1R in context‐reward associative learning and related dendritic morphology changes. To acquire CPP, a morphine group received saline or morphine 10 mg/kg s.c. on alternate days, while CPP controls received saline on all days, immediately before 8 daily place conditioning sessions. Post‐conditioning, morphine CPP mice expressed significantly higher place preference than saline mice. To induce extinction, mice were repeatedly exposed to the place conditioning environment in a drug‐free state. Morphine CPP mice received s.c. saline, 0.5 mg/kg SKF81297 (D1R agonist), or 0.8 mg/kg SKF81297 immediately after each extinction session, while controls received saline. After every two days of extinction training mice were tested for place preference. D1R agonist treatment inhibited extinction of place preference in a dose dependent manner. Mean place preference score of mice treated with the highest dose of agonist was double that of mice treated with saline. One day after the final place preference test brains were isolated and processed using Golgi‐Cox staining followed by digital tracing of accumbal neuron morphology. We previously showed that extinction of morphine CPP is associated with decreased dendritic complexity of neurons in the nucleus accumbens core. Since D1R agonist inhibits CPP extinction, we hypothesize that neurons from mice treated with 0.8 mg/kg SKF81297 will be prevented from undergoing extinction‐related changes, and will have higher dendritic complexity than controls.