Jacqueline Solomon and Dr. Scott Steffensen, College of Family, Home, and Social Science
Introduction:
Cocaine as a stimulant drug causes Dopamine (DA), a neurotransmitter, to be released in the Accumbens Nucleus (NAc). It accomplishes this by its well-known actions on the DA transporter (DAT). When the DAT is blocked, more DA stays in the synaptic cleft, leading to rewarding and pleasurable sensations. While in the synaptic cleft, DA undergoes excessive oxidation, giving rise to oxidative stress (OS) which causes neural damage. The OS has been shown in damaging the pleasure pathway and makes it so that addictive pathways are formed. In this research study we saw that Reactive Oxygen Species (ROS) Scavengers can eliminate the negative effects that the ROS cause on the NAc.
Methodology:
For this experiment we used Wistar male rats 250g- 400g. These rats are in compliance with the Institutional Animal Care and Use Committee (IACUC) regulations. Rats are model organisms for studying addiction because the neuronal pathways are similar to those in humans. The results in rats are analogous to those in humans. In this experiment we measured the base release of dopamine into the NAc by putting a stimulating electrode into the the Medial Forebrain Bundle, a projection to the NAc, and put a recording electrode in the NAc. After obtaining stable dopamine release recordings, we used a new drug, TEMPOL. This drug is a superoxide dismutase mimetic, which acts as an antioxidant that quenches the ROS. In our studies, we injected TEMPOL (100 mg/kg) intraperitoneally into rats and then exposed them to four doses of cocaine (0.1, 0.25, 0.5, and 1.0 mg/kg) via intravenous injection.
Results:
As we preformed these experiments we were able to see that the optimal dosage of TEMPOL to administer to see a significant decrease in DA release is 100 mg/kg. When we gave this dose we were able to see that instead of increased amounts of DA being released, we were able to suppress some of the DA released while Cocaine was administered. (Fig. 1)
Conclusion:
With the decreased release of DA we will have a decrease of DA left in the synaptic cleft which leads to a decrease in ROS. This decrease is very exciting and significant. If TEMPL can decrease the amount of DA released, then a potential cure to the addictive pathways of cocaine can be reversed. This opens many doors to the cure for drug addictions to help people overcome these habits that over take their lives.