Drugs of abuse inhibit striatal dopamine transmission evoked by prefrontal cortex inputs

• Autores: Shin, Jung Hoon; Adrover, Martín Federico; Authement, Michael; Álvarez, Verónica
• Año de publicación: 2019
• Idioma: inglés
• Tipo de recurso: documento de conferencia
• Materia: DOPAMINE; STRIATUM; PREFRONTAL CORTEX; DRUGS OF ABUSE
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Drugs of abuse target the reward system and have one common action in the brain: increasing dopamine (DA) in the striatum. Recently, it was shown that the activation of prefrontal cortex (PFC) inputs can evoke DA transients in the striatum, comparable to more conventional DA transients evoked by firing of midbrain DA neurons (DANs). In response to stimulation of glutamatergic inputs from the PFC, cholinergic interneurons fire action potentials and release acetylcholine (ACh), which in turns activate nicotinic ACh receptors on DA fibers and triggers DA release. It is yet unclear what is the function of this new form of DA transmission in vivo and the effects of drugs of abuse on it. Using in vitro voltammetry and transgenic mice with optogenetic techniques, DA transients were recorded in dorsal striatum by stimulating either PFC inputs or DAN fibers in the same brain slice. To our surprise, bath application of either cocaine, nicotine, ethanol, morphine, fentanyl, or THC all inhibited PFC-driven DA transients without affecting DAN-driven DA transients. Further experiments showed that while each drugs of abuse inhibit the PFC-driven DA transient, the mechanisms by which they do so differ. Furthermore, PFC-driven and DAN-driven DA transmission antagonized each other. When the stimulation of PFC fibers preceded stimulation of DAN fibers, the DAN-driven DA transient was depressed, and vice versa. These antagonistic effects were significantly reduced in the presence of cocaine. These findings encourage a reconsideration of how DA transmission in the striatum is affected by drugs of abuse and also reveal a novel interaction between two mechanisms of DA release that may be compromised by drugs of abuse.
Fil: Shin, Jung Hoon. National Institutes of Health; Estados Unidos
Fil: Adrover, Martín Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina
Fil: Authement, Michael. National Institutes of Health; Estados Unidos
Fil: Álvarez, Verónica. National Institutes of Health; Estados Unidos
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