Ventral pallidum GABA neurons bidirectionally control opioid relapse across rat behavioral models

Farrell, Mitchell R.; Ye, Qiying; Xie, Yiyan; Esteban, Jeanine Sandra D; Mahler, Stephen V.

doi:10.1016/j.addicn.2022.100026

Cited by 14 publications

(7 citation statements)

References 102 publications

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“…Inhibition of VP GABA neurons reduces relapse but does not affect re-acquisition, whereas inhibition of the mixed population of GABAergic and glutamatergic VP PV neurons reduces both alcohol relapse and re-acquisition (Prasad et al, 2020 ). In congruence with these findings, a recent study shows that chemogenetic stimulation of VP GABA neurons increases relapse to seeking of the opioid drug remifentanil in this model (Farrell et al, 2022 ).…”

Section: Part 2: Role Of the Ventral Pallidum In Motivated Behaviorssupporting

confidence: 69%

“…In addition, inhibiting the VP reduces drug-seeking when rats are returned to their initial safe training context where they first learned to self-administer cocaine (Farrell et al, 2019 ). Furthermore, chemogenetic inhibition of VP GABA neurons reduces cue-induced seeking of the opioid remifentanil upon returning rats to the safe context, whereas stimulation of VP GABA neurons increases drug-seeking in both the safe and the punished context (Farrell et al, 2022 ).…”

Section: Part 2: Role Of the Ventral Pallidum In Motivated Behaviorsmentioning

confidence: 99%

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Ventral pallidal regulation of motivated behaviors and reinforcement

Soares‐Cunha

Heinsbroek

2023

Front. Neural Circuits

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The interconnected nuclei of the ventral basal ganglia have long been identified as key regulators of motivated behavior, and dysfunction of this circuit is strongly implicated in mood and substance use disorders. The ventral pallidum (VP) is a central node of the ventral basal ganglia, and recent studies have revealed complex VP cellular heterogeneity and cell- and circuit-specific regulation of reward, aversion, motivation, and drug-seeking behaviors. Although the VP is canonically considered a relay and output structure for this circuit, emerging data indicate that the VP is a central hub in an extensive network for reward processing and the regulation of motivation that extends beyond classically defined basal ganglia borders. VP neurons respond temporally faster and show more advanced reward coding and prediction error processing than neurons in the upstream nucleus accumbens, and regulate the activity of the ventral mesencephalon dopamine system. This review will summarize recent findings in the literature and provide an update on the complex cellular heterogeneity and cell- and circuit-specific regulation of motivated behaviors and reinforcement by the VP with a specific focus on mood and substance use disorders. In addition, we will discuss mechanisms by which stress and drug exposure alter the functioning of the VP and produce susceptibility to neuropsychiatric disorders. Lastly, we will outline unanswered questions and identify future directions for studies necessary to further clarify the central role of VP neurons in the regulation of motivated behaviors.Significance: Research in the last decade has revealed a complex cell- and circuit-specific role for the VP in reward processing and the regulation of motivated behaviors. Novel insights obtained using cell- and circuit-specific interrogation strategies have led to a major shift in our understanding of this region. Here, we provide a comprehensive review of the VP in which we integrate novel findings with the existing literature and highlight the emerging role of the VP as a linchpin of the neural systems that regulate motivation, reward, and aversion. In addition, we discuss the dysfunction of the VP in animal models of neuropsychiatric disorders.

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Section: Part 2: Role Of the Ventral Pallidum In Motivated Behaviorssupporting

confidence: 69%

Section: Part 2: Role Of the Ventral Pallidum In Motivated Behaviorsmentioning

confidence: 99%

Ventral pallidal regulation of motivated behaviors and reinforcement

Soares‐Cunha

Heinsbroek

2023

Front. Neural Circuits

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“… 31 Another study showed that ventral pallidum GABA neurons control opioid relapses in opioid addiction. 32 …”

Section: Clinical and Research Consequencesmentioning

confidence: 99%

Factors Associated with Relapses in Alcohol and Substance Use Disorder

Yazıcı,

Bardakçı

2024

The Eurasian Journal of Medicine

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Alcohol and substance use disorder (ASUD) is a chronic condition featuring relapses and remissions. Due to their multifactorial nature, the causes of relapses in ASUD are not fully understood and it is important to update the information. Therefore, we aimed to provide an update on research examining factors associated with relapses, organized into sections. Factors such as early age of onset, dysfunction in the brain reward system, poor physical health, sleep disturbance, comorbid psychiatric disorders, severity of ASUD, craving, low self-efficacy, negative life events, and low socioeconomic status have been consistently shown to increase the relapse rate of ASUD. Conversely, factors such as positive family functioning, strong social support, treatment motivation and regular medication appear to decrease relapse rates. Studies on gender and genetic factors have yielded mixed results and no consistent relationship with relapses has been found. While pharmaceutical agents such as methadone, buprenorphine and naltrexone are effective in preventing relapse in opioid and alcohol use disorders; there are no agents proven to be effective in other substance use disorders. Psychotherapeutic approaches, including motivational interviewing, cognitive behavioral therapy, 12-step programs and contingency management have been demonstrated to be effective. The treatment of addiction to substances is intricate and necessitates biopsychosocial interventions. However, despite all treatments, high relapse rates indicate the necessity for social support and rehabilitation services. In the light of the data obtained, the factors affecting relapses in patients with ASUD can be determined and appropriate interventions and therapeutic approaches can be used to prevent relapses.

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“…Together, these findings might suggest that VP GABA neurons control food-seeking but not consumption, which would be surprising considering the prior work discussed above (Covelo et al, 2014;Cromwell and Berridge, 1993;Stratford and Wirtshafter, 2013). Yet, the internal state of animals is known to impact VP GABA responses to reward and reward-seeking (Farrell et al, 2022(Farrell et al, , 2021Stephenson-Jones et al, 2020). Additionally, VP manipulations have been shown to have differential influence over different macronutrients (Covelo et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Ventral pallidal GABAergic neurons drive consumption in male, but not female rats

Scott,

Paulson,

Prill

et al. 2024

Preprint

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Food intake is controlled by multiple converging signals: hormonal signals that provide information about energy homeostasis, but also hedonic and motivational aspects of food and food cues that can drive non-homeostatic or hedonic feeding. The ventral pallidum (VP) is a brain region implicated in the hedonic and motivational impact of food and foods cues, as well as consumption of rewards. Disinhibition of VP neurons has been shown to generate intense hyperphagia, or overconsumption. While VP gamma-Aminobutyric acidergic (GABA) neurons have been implicated in cue-elicited reward seeking and motivation, the role of these neurons in the hyperphagia resulting from VP activation remains unclear. Here, we used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to activate or inhibit VP GABA neurons in sated male and female rats during chow and sucrose consumption. We found that activation of VP GABA neurons increases consumption of chow and sucrose in male rats, but not female rats. We also found that, while inhibition of VP GABA neurons tended to decrease sucrose consumption, this effect was not statistically significant. Together, these findings suggest that activation of VP GABA neurons can stimulate consumption of routine or highly palatable rewards selectively in male rats.

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Ventral pallidum GABA neurons bidirectionally control opioid relapse across rat behavioral models

Cited by 14 publications

References 102 publications

Ventral pallidal regulation of motivated behaviors and reinforcement

Ventral pallidal regulation of motivated behaviors and reinforcement

Factors Associated with Relapses in Alcohol and Substance Use Disorder

Ventral pallidal GABAergic neurons drive consumption in male, but not female rats

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