Neural Circuits and Systems Neuroscience
Author: Maria Flavia Barbano | Email: maria.barbano@nih.gov
Flavia Barbano1°, Jia Qi1°, Orlando Espinoza1°, Uzma Mohammad1°, Marcos Candido1°, Marisela Morales1°
1° National Institute on Drug Abuse (NIDA/NIH)
The dorsal raphe nucleus (DR) contains glutamatergic neurons that express the vesicular glutamate transporter type 3 (VGluT3). We have demonstrated that DR-VGluT3 neurons establish synapses with ventral tegmental area (VTA) dopaminergic neurons. Activation of this pathway induces release of dopamine in the nucleus accumbens and is rewarding. Here, we determined whether DR-VGluT3 inputs to the VTA play a role in cocaine seeking behavior, measured by conditioned place preference (CPP) and self-administration (SA). We expressed Channelrhodopsin in DR-VGluT3 neurons in mice and evoked the release of glutamate in the VTA by photostimulation. We tested the behavior of these mice using a CPP procedure, to evaluate the role of VTA glutamate release after extinction of cocaine CPP. VTA photostimulation of DR-VGluT3 inputs induced reinstatement of cocaine CPP but did not induce reinstatement of food-seeking behavior. We next determined whether VTA glutamate release from the DR modifies stress- or priming-induced reinstatement of cocaine CPP or cocaine-seeking. We injected Halorhodopsin (Halo) in DR-VGluT3 neurons and implanted bilateral optic fibers in the VTA. Control mice reinstated cocaine CPP and cocaine-seeking after stress or a cocaine priming injection. In contrast, reinstatement was not observed in Halo mice. From these findings, we concluded that VTA release of glutamate from DR-VGluT3 fibers plays a critical and unexpected role in the reinstatement of cocaine-seeking behavior