Authors: Lauren Ford, Joel Woolley, Ryan Powers, Paulina Medellin, Hillary Wadsworth, Jordan Yorgason
Mentors: Jordan Yorgason
Insitution: Brigham Young University
Women prescribed psychostimulants have self-reported changes in drug efficacy that coincide with menstrual cycling. Furthermore, cocaine and amphetamine effects on dopamine (DA) transmission are more potent in female rodents, an effect that has been linked to cycling hormone levels. However, it is unknown if changes to DA transmission vary by specific psychostimulant, and striatal DA transmission has not yet been well characterized across the estrous cycle. The present study considers dopamine release and reuptake kinetics across various stages of the estrous cycle in the nucleus accumbens (NAc), a key region for dopamine-mediated learning. The effects of cocaine, methamphetamine, and methylphenidate on female dopamine transmission are examined using slice voltammetry.
Our data shows that compared to a male control group, baseline (pre-drug) dopamine release in the NAc was lower in females overall, but not at all estrous stages. Applying increasing concentrations of cocaine or methylphenidate revealed similar patterns of enhanced, then diminished release in all mice. Methamphetamine decreased NAc dopamine release similarly in both males and females, but females in estrus were more affected than males, and those in met/diestrus less. Methamphetamine also slowed dopamine uptake in all mice, and at lower concentrations than cocaine or methylphenidate.
We find minimal sex differences between cocaine and methylphenidate effects in the NAc, suggesting that the underlying cause of their observed behavioral sex differences may be specific to other striatal regions. On the other hand, methamphetamine-induced DA release fluctuates distinctly with the estrous cycle and peaks when estrogen levels are at their highest, indicating that estrogen and methamphetamine mechanisms share a target in NAc DA terminals that cocaine and methylphenidate do not. This work refines our understanding of DA transmission in females and indicates potential future directions for understanding female psychostimulant abuse.