Dopamine circuit function in the nucleus accumbens (NAc) and ventral tegmental area (VTA) is implicated in the reinforcing effects of drugs of abuse including opioids. Previous investigations have reported sensitization of the VTA after morphine conditioning. Further characterization of sensitivity changes to the mu receptor and other receptors in the opioid family as well as further characterization of intra-VTA circuitry is necessary. Previous research has also demonstrated that women often use drugs differently and that addiction treatment is not equally effective between sexes thus requiring further invesigation into sex differences in the addiction pathway. Our data supports the hypothesis that mu opioid receptor desensitization occurs during acute and prolonged exposure to opioids such as morphine, which may have long lasting effects on dopamine circuit function. We performed fast scan cyclic voltammetry (FSCV) in morphine-conditioned mice. We report that in NAc brain slices, morphine has no apparent direct effects on dopamine release. In contrast, morphine bath application increases VTA dopamine release, which is reversed by naloxone. Interestingly, morphine induced increases in VTA dopamine release were greater in morphine vs saline conditioned mice, supporting a model of circuit sensitization. We report that this circuit sensitization is supported by sensitization of mu opioid receptors in both sexes and delta opioid receptors in females. This is possibly biologically counteracted by a desensitization of kappa opioid receptors. Surprisingly, blocking voltage gated potassium channels resulted in a switch in morphine effects, where morphine reduced VTA dopamine release. Morphine treated mice had reduced sensitivity to morphine effects on dopamine release in the presence of potassium channel blockers, suggesting that potassium channels possibly underlie the increases in sensitivity observed in morphine conditioned mice.
University / Institution: Brigham Young University
Format: In Person
SESSION B (10:45AM-12:15PM)
Area of Research: Science & Technology
Faculty Mentor: Jordan Yorgason