Author(s): Zachary Valentine, Chase Seiter
Mentor(s): Jordan Yorgason
Institution BYU
This project explores the involvement of granulocyte-colony stimulating factor (G-CSF) in ethanol-induced dopamine (DA) adaptations. Ethanol has been demonstrated to increase the firing rate of dopamine neurons in the ventral tegmental area (VTA) with increased potency when administered in the periphery, indicating the presence of an intermediate step or substrate in its mechanism of action. We propose that the immune system serves as a potential regulatory modulator in this context. G-CSF, an immune signaling molecule, has previously been shown to enhance the effects of cocaine on DA release and reuptake. Given that dopamine terminals can be regulated by local cholinergic interneurons via nicotinic acetylcholine receptors, cholinergic inputs emerge as a crucial potential target for neuroimmune effects. Our hypothesis suggests that ethanol induces peripheral immune activation, leading to G-CSF release, thereby acutely enhancing DA neurons either directly or indirectly through increased cholinergic activity. Additionally, we hypothesize that prolonged alcohol exposure weakens G-CSF release, resulting in diminished effects on dopamine terminals and associated circuitry.