The Ventral Pallidum: Proposed Integrator of Positive and Negative Factors in Cocaine Abuse

James, Morgan H.; Aston‐Jones, Gary

doi:10.1016/j.neuron.2016.09.042

Cited by 5 publications

(4 citation statements)

References 12 publications

(31 reference statements)

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“…Restoration of function at D1 NAc-VP synapses eliminated cocaine locomotor sensitization, while rescue at D2 NAc-VP synapses reversed cocaine withdrawalinduced anhedonia, suggesting that NAc D1 versus D2 MSN efferents to VP regulate distinct behavioral states [82]. This work highlights not only the differential impact of D1 versus D2 MSN circuits, but also the importance of the NAc-VP circuit in cocaine-related behaviors, a topic of great recent interest [83][84][85][86][87].…”

Section: Nac Msn Stimulationmentioning

confidence: 71%

Reward Circuitry in Addiction

2017

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Understanding the brain circuitry that underlies reward is critical to improve treatment for many common health issues, including obesity, depression, and addiction. Here we focus on insights into the organization and function of reward circuitry and its synaptic and structural adaptations in response to cocaine exposure. While the importance of certain circuits, such as the mesocorticolimbic dopamine pathway, are well established in drug reward, recent studies using genetics-based tools have revealed functional changes throughout the reward circuitry that contribute to different facets of addiction, such as relapse and craving. The ability to observe and manipulate neuronal activity within specific cell types and circuits has led to new insight into not only the basic connections between brain regions, but also the molecular changes within these specific microcircuits, such as neurotrophic factor and GTPase signaling or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor function, that underlie synaptic and structural plasticity evoked by drugs of abuse. Excitingly, these insights from preclinical rodent work are now being translated into the clinic, where transcranial magnetic simulation and deep brain stimulation therapies are being piloted in human cocaine dependence. Thus, this review seeks to summarize current understanding of the major brain regions implicated in drug-related behaviors and the molecular mechanisms that contribute to altered connectivity between these regions, with the postulation that increased knowledge of the plasticity within the drug reward circuit will lead to new and improved treatments for addiction.

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Section: Nac Msn Stimulationmentioning

confidence: 71%

Reward Circuitry in Addiction

2017

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“…As a key node in the ventral basal ganglia, the VP integrates inputs from NAc D 1 R and D 2 R neurons and sends outputs to LH, VTA, LHb, and back to NAc. 20 , 35 The VP plays a crucial role in the regulation of motivation, 11 reward seeking, 12 , 13 , 14 , 36 decision-making, 37 addiction, 38 stress, 15 behavioral avoidance, 39 and depression-related behaviors. 16 , 17 Glutamatergic and GABAergic VP neurons might mediate the opposing regulation of “positive” and “negative” behaviors.…”

Section: Discussionmentioning

confidence: 99%

Ventral pallidal glutamatergic neurons regulate wakefulness and emotion through separated projections

Luo

Chen

et al. 2023

iScience

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“…Inhibition of MSNs projecting to the VP and the resulting suppression of GABA release, is common to various drugs of abuse and could be important for their reinforcing properties. Several drugs of abuse have been shown to suppress extracellular levels of GABA or inhibit GABAergic evoked inhibitory postsynaptic potentials (eIPSCs) in the VP. − Recent work suggests that the VP is at a strategic anatomical position to integrate D 1 - and D 2 -MSN activity and relay this information to key motivational circuits. ,,, Findings from Creed et al suggests that the VP may be a site of convergence for drug-evoked synaptic changes that contribute to both positive and negative symptoms following cocaine experience . In addition to changes in synaptic plasticity, administration of psychostimulants has been shown to increase DA release within the VP .…”

Section: Mesolimbic Dopamine In Drug and Food Reward: Homeostatic And...mentioning

confidence: 99%

Shared Behavioral and Neurocircuitry Disruptions in Drug Addiction, Obesity, and Binge Eating Disorder: Focus on Group I mGluRs in the Mesolimbic Dopamine Pathway

Yohn

Galbraith

Calipari

et al. 2019

ACS Chem. Neurosci.

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Accumulated data from clinical and preclinical studies suggest that, in drug addiction and states of overeating, such as obesity and binge eating disorder (BED), there is an imbalance in circuits that are critical for motivation, reward saliency, executive function, and self-control. Central to these pathologies and the extensive topic of this Review are the aberrations in dopamine (DA) and glutamate (Glu) within the mesolimbic pathway. Group I metabotropic glutamate receptors (mGlus) are highly expressed in the mesolimbic pathway and are poised in key positions to modulate disruptions in synaptic plasticity and neurotransmitter release observed in drug addiction, obesity, and BED. The use of allosteric modulators of group I mGlus has been studied in drug addiction, as they offer several advantages over traditional orthosteric agents. However, they have yet to be studied in obesity or BED. With the substantial overlap between the neurocircuitry involved in drug addiction and eating disorders, group I mGlus may also provide novel targets for obesity and BED.

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The Ventral Pallidum: Proposed Integrator of Positive and Negative Factors in Cocaine Abuse

Abstract: In this issue of Neuron, Creed et al. (2016) describe how cocaine produces divergent forms of plasticity at synapses between specific neurons in nucleus accumbens and ventral pallidum, and how these changes are associated with positive and negative reward behaviors.

Cited by 5 publications

References 12 publications

Reward Circuitry in Addiction

Reward Circuitry in Addiction

Ventral pallidal glutamatergic neurons regulate wakefulness and emotion through separated projections

Shared Behavioral and Neurocircuitry Disruptions in Drug Addiction, Obesity, and Binge Eating Disorder: Focus on Group I mGluRs in the Mesolimbic Dopamine Pathway

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