Involvement of Infralimbic Prefrontal Cortex but not Lateral Habenula in Dopamine Attenuation After Chronic Mild Stress
Open accessAbstract
Emerging evidence supports a role for dopamine in major depressive disorder (MDD). We recently reported fewer spontaneously active ventral tegmental area (VTA) dopamine neurons (ie, reduced dopamine neuron population activity) in the chronic mild stress (CMS) rodent model of MDD. In this study, we examined the role of two brain regions that have been implicated in MDD in humans, the infralimbic prefrontal cortex (ILPFC)-that is, rodent homolog of Brodmann area 25 (BA25), and the lateral habenula (LHb) in the CMS-induced attenuation of dopamine neuron activity. The impact of activating the ILPFC or LHb was evaluated using single-unit extracellular recordings of identified VTA dopamine neurons. The involvement of each region in dopamine neuron attenuation following 5-7 weeks of CMS was then evaluated by selective inactivation. Activation of either ILPFC or LHb in normal rats potently suppressed dopamine neuron population activity, but in unique patterns. ILPFC activation selectively inhibited dopamine neurons in medial VTA, which were most impacted by CMS. Conversely, LHb activation selectively inhibited dopamine neurons in lateral VTA, which were unaffected by CMS. Moreover, only ILPFC inactivation restored dopamine neuron population activity to normal levels following CMS; LHb inactivation had no restorative effect. These data suggest that, in the CMS model of MDD, the ILPFC is the primary driver of diminished dopamine neuron responses. These findings support a neural substrate for ILPFC/BA25 linking affective and motivational circuitry dysfunction in MDD.
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NMDA infusions into ILc reduced spontaneous firing of DA neurons in the medial VTA.
“Consistent with the latter, NMDA infusions into ILc reduced spontaneous firing of DA neurons in the medial VTA [139].”
From Prefrontal cortex and depression (2022) · cites this paper as [139]
In one case of ILc, its inactivation selectively blocked the effects of chronic mild stress on reward-related dopamine activity.
“In one case of ILc, its inactivation selectively blocked the effects of chronic mild stress on reward-related dopamine activity [139].”
From Prefrontal cortex and depression (2022) · cites this paper as [139]
In chronic stress-induced depression, the blunting occurs primarily in the neurons projecting to the ventromedial striatum, where reward-related variables are processed.
“whereas in chronic stress-induced depression (Holly and Miczek, 2016), the blunting occurs primarily in the neurons projecting to the ventromedial striatum (Moreines et al., 2017), where reward-related variables are processed.”
From The effects of psychosocial stress on dopaminergic function and the acute stress response (2019) · cites this paper as Moreines et al., 2017
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- Authors
- Moreines, J. L., Owrutsky, Z. L., & Grace, A. A.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Moreines, Jared L
- Venue
- Neuropsychopharmacology
- Published
- 2016-11-04
- Volume
- 42
- Issue
- 4
- Pages
- 904-913
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC5312072
- OpenAlex
- W2547816908
- Cited by
- 93
- References
- 51
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 6 · 2023: 12 · 2022: 11 · 2021: 17 · 2020: 4 · 2019: 13 · 2018: 12 · 2017: 9
- FWCI
- 6.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (2r01mh057440-26a1, 5r01mh101180-05)
- National Institute of Mental Health (R01-MH101180, R01-MH057440, F30MH105199)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- infralimbic cortex, lateral habenula, dopaminergic neurons, ventral tegmental area, chronic mild stress, major depressive disorder, neural circuits, depression model
- MeSH terms
- Animals, Depressive Disorder, Major, Major Depressive Disorder, Disease Models, Animal, Dopamine, Male, Stress, Psychological, Rats, Sprague-Dawley, Prefrontal Cortex, Ventral Tegmental Area, Habenula, Rats, Dopaminergic Neurons
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