The mesolimbic dopamine pathway is important for reward and motivation. However, neurobiological mechanisms behind these behaviors are complicated. This animal study gives us insight about how such mechanisms work. Here, we test how mu opioid receptors (MORs) expressed on cholinergic interneurons mediate the reward seeking behaviors for a natural reward (sucrose) to investigate the possible relationship between MORs and sucrose self administration. The knockout line of mice consists of the genetic deletion of MOR on cholinergic cells. For the methods, the ChAT-MOR mice were bred on a C57BL/6J background. A total of 16 mice were used, and were divided into a control (wildtype) and an experimental (knockout) group based on their genotype. Experiment 1 tested the reward seeking pathway using sucrose fading by changing the concentration of sucrose from 10% to 2%. Experiment 2 analyzed motivation through a progressive ratio schedule. Experiment 3 investigated the effects of increasing concentrations of quinine (0, 100, 250, 500μM) using a 5% sucrose concentration. For experiment 1, we hypothesized that due to the intact ChAT-MOR gene, the wildtype mice would show greater motivation at all levels of sucrose concentration in comparison to the knockout mice. For experiment 2, we hypothesized that the wildtype mice would have a higher breakpoint in comparison to the knockout mice. For experiment 3, we hypothesized that the knockout mice would demonstrate greater aversion resistance at all concentrations. When analyzing entries into the reward receptacle, a 3-way ANOVA revealed a significant interaction between sex and genotype. Specifically, there was a main effect of the genotype for males only. For rewards earned and number of nose pokes, the 3-way ANOVA interaction between genotype and sex and the interaction between concentration, genotype and sex were near the threshold of significance. Regarding quinine aversion, the 3-way ANOVA interaction between quinine concentration and sex demonstrated significance for the males. However, the 3-way ANOVA for activity level did not provide any significant interactions. These results suggest that MOR expression on striatal cholinergic interneurons has the potential to affect reward-seeking behaviors, including important sex differences in this circuit. Nonetheless, our experiment was limited to the number of mice provided. Going forward, researchers should test the ChAT-MOR knockout (HET) males and measure their motivation for reward using opiate-drugs instead of sucrose.
Author(s): Mia Sooch, Biology and Premedical Studies Major
HaoFeng Tian, Psychology and Neuroscience Major
Charlotte Roemer, Psychology Major
Brenda Martinez, Medical Laboratory Science and Premedical Studies Major
Advisor(s): Anna Radke, Department of Psychology
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