Major
Neuroscience
Anticipated Graduation Year
2021
Access Type
Open Access
Abstract
The reward-seeking behavior associated with human psychostimulant drug addiction are driven by dopamine (DA) neurotransmission in the ventral tegmental area (VTA). The ability of psychostimulants to increase mesoaccumbal DA signaling is critical for their ability to promote appetitive behaviors including exploratory behaviors (locomotion) and self-administration. Sensitization results from frequent and repeated drug use and is characterized by persistent neuroadaptations including changes in glutamate receptor signaling at the VTA. These adaptations are important for turning drug use from casual to compulsive and addictive. The VTA receives signaling from many brain regions, it is unlikely they all contribute to this potentiated glutamate signaling during cocaine exposure. The laterodorsal tegmental nucleus (LDTg) provides a source of glutamate input to the VTA that excites DA signaling. In previous studies using VGluT2::Cre transgenic mice, inhibition of LDTg glutamate inputs at the VTA using optogenetics blocks the development of cocaine locomotor sensitization. Here we tested whether inhibition of LDTg glutamate inputs at the VTA blocks the development of neurochemical sensitization of nucleus accumbens (NAc) DA which is known to accompany the development of locomotor sensitization. We show that inhibition of these inputs at the VTA blocks the neurochemical sensitization of NAc DA suggesting that LDTg glutamate inputs at the VTA may be an important target for interventions aimed at preventing the transition from casual to addictive drug use.
Faculty Mentors & Instructors
Stephan Steidl, Associate Professor Department of Psychology
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Inhibition of laterodorsal tegmental nucleus glutamate inputs to the ventral tegmental area blocks neurochemical sensitization in mice
The reward-seeking behavior associated with human psychostimulant drug addiction are driven by dopamine (DA) neurotransmission in the ventral tegmental area (VTA). The ability of psychostimulants to increase mesoaccumbal DA signaling is critical for their ability to promote appetitive behaviors including exploratory behaviors (locomotion) and self-administration. Sensitization results from frequent and repeated drug use and is characterized by persistent neuroadaptations including changes in glutamate receptor signaling at the VTA. These adaptations are important for turning drug use from casual to compulsive and addictive. The VTA receives signaling from many brain regions, it is unlikely they all contribute to this potentiated glutamate signaling during cocaine exposure. The laterodorsal tegmental nucleus (LDTg) provides a source of glutamate input to the VTA that excites DA signaling. In previous studies using VGluT2::Cre transgenic mice, inhibition of LDTg glutamate inputs at the VTA using optogenetics blocks the development of cocaine locomotor sensitization. Here we tested whether inhibition of LDTg glutamate inputs at the VTA blocks the development of neurochemical sensitization of nucleus accumbens (NAc) DA which is known to accompany the development of locomotor sensitization. We show that inhibition of these inputs at the VTA blocks the neurochemical sensitization of NAc DA suggesting that LDTg glutamate inputs at the VTA may be an important target for interventions aimed at preventing the transition from casual to addictive drug use.