Cell type-specific loss of BDNF signaling mimics optogenetic control of cocaine reward
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BDNF, Dopamine, and Cocaine Reward: The nucleus accumbens plays a crucial role in mediating the rewarding effects of drugs of abuse. Different subpopulations of nucleus accumbens projection neurons exhibit balanced but antagonistic influences on their downstream outputs and behaviors. However, their roles in regulating reward behaviors remains unclear. Lobo et al. (p. 385 ) evaluated the roles of the two subtypes of nucleus accumbens projection neurons, those expressing dopamine D1 versus D2 receptors, in cocaine reward. Deleting TrkB, the receptor for brain-derived neurotrophic factor, selectively in each cell type, and selectively controlling the firing of each cell type using optogenetic techniques allowed for confirmation that D1- and D2-containing neurons produced opposite effects on cocaine reward.
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TrkB is enriched in D2 medium spiny neurons.
“TrkB is enriched in D2-MSNs and BDNF signaling through TrkB has different roles in NAc MSN subtypes in psychostimulant and opiate motivation (26, 70), but depression-related BDNF signaling in MSN subtypes is unclear.”
From Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression (2017) · cites this paper as [26]
BDNF signaling through TrkB has different roles in nucleus accumbens medium spiny neuron subtypes in psychostimulant and opiate motivation.
“TrkB is enriched in D2-MSNs and BDNF signaling through TrkB has different roles in NAc MSN subtypes in psychostimulant and opiate motivation (26, 70), but depression-related BDNF signaling in MSN subtypes is unclear.”
From Emerging Role for Nucleus Accumbens Medium Spiny Neuron Subtypes in Depression (2017) · cites this paper as [26]
Inhibition of striatal D2R or activation of D1R-expressing striatal neurons enhances sensitivity to the rewarding effects of drugs.
“inhibition of striatal D2R or activation of D1R-expressing striatal neurons (which mediate signalling in the striatal direct pathway) enhance the sensitivity to the rewarding effects of drugs (71–73).”
From Obesity and addiction: Neurobiological overlaps (2013) · cites this paper as [73]
Optogenetic stimulation of D1-type medium spiny neurons in rodents enhances reward driven behaviors, whereas stimulations of D2-type medium spiny neurons results in freezing behavior.
“For example, optogenetic stimulation of D1-type medium spiny neurons in rodents enhances reward driven behaviors, whereas stimulations of D2-type medium spiny neurons results in freezing behavior (Lobo et al., 2010).”
From Dopaminergic reward sensitivity can promote adolescent health: a new perspective on the mechanism of ventral striatum activation (2016) · cites this paper as Lobo et al., 2010
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- Authors
- Lobo, M. K., Covington, H. E., Chaudhury, D., Friedman, A. K., Sun, H., Damez-Werno, D., Dietz, D. M., Zaman, S., Koo, J. W., Kennedy, P. J., Mouzon, E., Mogri, M., Neve, R. L., Deisseroth, K., Han, M.-H., & Nestler, E. J.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Stanford University (US)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Nestler, Eric J.
- ORCID
- Venue
- Science
- Published
- 2010-10-15
- Volume
- 330
- Issue
- 6002
- Pages
- 385-390
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3011229
- OpenAlex
- W2079590230
- Cited by
- 880
- References
- 42
- Citations by year
- 2026: 27 · 2025: 44 · 2024: 44 · 2023: 57 · 2022: 43 · 2021: 62 · 2020: 40 · 2019: 59 · 2018: 60 · 2017: 57 · 2016: 77 · 2015: 57 · 2014: 64 · 2013: 71 · 2012: 63
- FWCI
- 24.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01MH051399)
- National Institute on Drug Abuse (T32DA007135, P01DA008227, R01DA007359, R01DA014133)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- cocaine reward, nucleus accumbens, TrkB, BDNF signaling, dopamine D1 receptor, dopamine D2 receptor, optogenetic manipulation, neuronal excitability, cell type-specific gene deletion, reward systems
- MeSH terms
- Channelrhodopsins, Animals, Behavior, Animal, Cocaine, Conditioning, Psychological, Light, Mice, Transgenic, Models, Biological, Motor Activity, Neurons, Nucleus Accumbens, Reward, RNA, Messenger, Signal Transduction, Receptors, Dopamine D1, Receptors, Dopamine D2, Brain-Derived Neurotrophic Factor, Mitogen-Activated Protein Kinase 1, Cocaine-Related Disorders, Receptor, trkB, Mitogen-Activated Protein Kinase 3, Mice
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