Small, Christina; Obray, J Daniel; Steffensen, Scott (Brigham Young University)
Faculty Advisor: Steffensen, Scott (Family, Home, and Social Sciences; Psychology)
Recent studies have shown that administration of dopamine in the periphery (outside of the brain) produces a robust enhancement of dopamine release in the nucleus accumbens and alleviates cognitive deficits associated with schizophrenia-like and attention deficit hyperactivity disorder (ADHD)-like phenotypes in rodent models. Despite this, the mechanism whereby peripheral administration of dopamine produces these effects is unknown as dopamine does not cross the blood brain barrier. Activation of dopamine 2 receptors on circulating leukocytes encourages extravasation and can trigger production and release of cytokines such as TNF-_ and IL-10 as well as IL-1_. IL-1_ and IL-10 are both known to enhance dopamine release. In this study we demonstrate that the effects of intravenous dopamine on dopamine release in the NAc are mediated by peripheral dopamine 2 receptors. Additionally, we show that intravenous dopamine is rewarding and that these rewarding effects can be blocked by antagonism of peripheral dopamine 2 receptors. As many drugs of abuse enhance plasma dopamine levels this research elucidates a secondary pathway which may play a role in the development of substance use disorders.