Amygdala-Ventral Pallidum Pathway Decreases Dopamine Activity After Chronic Mild Stress in Rats

Chang, Chung-Yi; Grace, Anthony A.

doi:10.1016/j.biopsych.2013.09.020

Cited by 192 publications

(231 citation statements)

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“…In animal models of MDDs, in which anhedonia is a core symptom, a decrease in DA neuron activity in the VTA has been described by our group (Belujon and Grace, 2014;Chang and Grace, 2014) and others (Tye et al, 2013). Indeed, we have shown previously in the CMS model (Chang and Grace, 2014) a decrease in DA activity in the VTA, as well as an increase in immobility time, in the FST.…”

Section: Discussionsupporting

confidence: 52%

“…Indeed, we have shown previously in the CMS model (Chang and Grace, 2014) a decrease in DA activity in the VTA, as well as an increase in immobility time, in the FST. Moreover, in the learned helplessness model, a decrease in DA activity, as well as failure to escape, has been described (Belujon and Grace, 2014).…”

Section: Discussionmentioning

confidence: 56%

“…Therefore, changes in PFC function after psychostimulant administration is likely to have an influence on information processing in downstream structures such as the BLA, as previously described in animal models of depression (Chang and Grace, 2014;Moreines et al, 2014). It should be noted that the BLA sends very few direct projections to DA neurons in the VTA, suggesting intermediate structure, such as the ventral pallidum (VP) (Chang and Grace, 2014), in mediating these effects. Indeed, the BLA sends direct excitatory projections to the VP (Maslowski-Cobuzzi and Napier, 1994), a key structure in saline dPBS (7) saline TTX (7) amphetamine dPBS (5) amphetamine TTX (7) 0.0 medial central lateral 0.5…”

Section: Discussionmentioning

confidence: 79%

“…The Amphetamine-Induced Decrease in DA Neuron Activity is Reversed by Inactivation of the BLA We have shown previously in the CMS animal model of depression that the decreased in DA activity in the VTA was due to hyperactivity of the BLA (Chang and Grace, 2014). As BLA neurons are also activated during drug selfadministration and by stimuli previously paired with intravenous delivery of the psychostimulant cocaine (Carelli et al, 2003), we tested whether the decrease in DA neuron activity after withdrawal from acute amphetamine was also dependent on the BLA (Figure 3).…”

Section: Da Activity and Immobility In The Fst Returned To Baseline 7mentioning

confidence: 93%

“…In animal models of depression, such as the chronic mild stress (CMS) and the learned helplessness model, we have shown previously that there is a decrease in DA activity that could be reversed by inactivation of the basolateral amygdala (BLA) (Chang and Grace, 2014) and injection of the N-methyl-D-aspartate (NMDA) antagonist and novel antidepressant ketamine (Belujon and Grace, 2014). In drug addiction, many studies have focused on the negative affective state after repeated drug administration in humans (Leventhal et al, 2008) and animal models (Der-Avakian and Markou, 2010); however, this condition appears even after a drug is taken for the first time (Koob and Le Moal, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Withdrawal from Acute Amphetamine Induces an Amygdala-Driven Attenuation of Dopamine Neuron Activity: Reversal by Ketamine

Belujon

Jakobowski

Dollish

et al. 2015

Neuropsychopharmacol

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Drug addiction is a chronic disorder characterized by a cycle composed of drug seeking, intoxication with drug taking and withdrawal associated with negative affect. Numerous studies have examined withdrawal/negative affect after chronic use; however, very few have examined the effect of acute administration on the negative affective state after acute drug withdrawal. One dose of amphetamine was injected into Sprague-Dawley rats. Despair behavior using the modified forced swim test (FST) and dopamine (DA) activity in the ventral tegmental area using in vivo electrophysiological recordings were studied 18, 48 and 72 h after injection of amphetamine. The effects of inactivation of the basolateral amygdala (BLA) and ketamine administration on VTA DA neuron activity and passivity in the modified FST were examined. Eighteen hours following amphetamine withdrawal, there was a substantial decrease in the number of active DA neurons, as well as an increase in time spent immobile in the modified FST, which returned to baseline after 72 h. Inactivation of the BLA after acute amphetamine prevented the decrease in DA neuron tonic activity. Injection of ketamine also prevented the decrease in DA population activity but had no effect on immobility measured in the modified FST. The data support a model in which the negative affective state following acute amphetamine withdrawal is associated with a decrease in DA neuron population activity, driven by hyperactivity of the BLA. Although ketamine reversed the hypodopaminergic state following withdrawal, the failure to reduce immobility in the modified FST indicates that different processes underlying negative emotional state may exist between depression and drug withdrawal.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 79%

Section: Da Activity and Immobility In The Fst Returned To Baseline 7mentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Withdrawal from Acute Amphetamine Induces an Amygdala-Driven Attenuation of Dopamine Neuron Activity: Reversal by Ketamine

Belujon

Jakobowski

Dollish

et al. 2015

Neuropsychopharmacol

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Effects of city living on the mesolimbic reward system—An fmri study

Krämer

Diekhof

Gruber

2017

Human Brain Mapping

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Based on higher prevalence rates of several mental disorders for city dwellers, psychosocial stress effects of urban living have been proposed as an environmental risk factor contributing to the development of mental disorders. Recently, it was shown that amygdala activation differs between city dwellers and rural residents in response to a cognitive-social stressor. Besides its influence on the amygdala, chronic stress also affects mesocorticolimbic brain regions involved in reward processing, and stress-related dysregulation of the mesocorticolimbic dopamine system is thought to contribute to onset and manifestation of psychiatric disorders. Here, we investigated differences in reward systems functioning in 147 healthy subjects living either in cities or in less urban areas by means of functional magnetic resonance imaging during performance of the desire-reason-dilemma paradigm, which permits a targeted investigation of bottom-up activation and top-down regulation of the reward circuit. Compared with subjects from less urban areas, city dwellers showed an altered activation and modulation capability of the midbrain (VTA) dopamine system. City dwellers also revealed increased responses in other brain regions involved in reward processing and in the regulation of stress and emotions, such as amygdala, orbitofrontal, and pregenual anterior cingulate cortex. These results provide further evidence for effects of an urban environment on the mesolimbic dopamine system and the limbic system which may increase the risk to develop mental disorders. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

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The role of amygdala‐ventral pallidum pathway in depression‐like behaviors in male mice

Guo,

Gao

et al. 2023

J of Neuroscience Research

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The basolateral amygdala (BLA) appears to serve an important function in the pathophysiology of depression. Depressive symptoms, such as anhedonia are largely caused by dysfunction in the brain's reward system, in which the ventral pallidum (VP) participates in by controlling dopamine release. However, the role of the BLA‐VP pathway in the development of depression remains poorly understood. To investigate this pathway, we employed the Chronic Unpredictable Mild Stress (CUMS) mouse model, in which we injected retroAAV expressing GFP‐Cre into the VP and AAV expressing hM4Di‐mCherry into the BLA. We then used CNO to activate the Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) for all behavioral tests. The CUMS procedure resulted in significant depression symptoms such as decreased sucrose preference, limited weight gain, decreased immobile latency, and increased immobile time in the forced swim and tail suspension tests. Inhibition of the BLA‐VP glutamatergic projections reversed these depression‐like behaviors. We found that suppressing the BLA‐VP circuitry had beneficial effects on CUMS‐induced depression‐like behaviors such as anorexia, anhedonia, and despair. Specifically, upon suppression of glutamatergic projections in the BLA‐VP circuitry, these depression‐like behaviors were significantly alleviated, which highlights the vital role of this circuitry in the development of depression. Furthermore, the beneficial effects of suppressing this circuitry seem to be associated with the brain's reward system, warranting further investigation.

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Amygdala-Ventral Pallidum Pathway Decreases Dopamine Activity After Chronic Mild Stress in Rats

Cited by 192 publications

References 50 publications

Withdrawal from Acute Amphetamine Induces an Amygdala-Driven Attenuation of Dopamine Neuron Activity: Reversal by Ketamine

Withdrawal from Acute Amphetamine Induces an Amygdala-Driven Attenuation of Dopamine Neuron Activity: Reversal by Ketamine

Effects of city living on the mesolimbic reward system—An fmri study

The role of amygdala‐ventral pallidum pathway in depression‐like behaviors in male mice

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