The Role of the Lateral Habenula in Punishment

Jean-Richard-dit-Bressel, Philip; McNally, Gavan P.

doi:10.1371/journal.pone.0111699

Cited by 21 publications

(17 citation statements)

References 33 publications

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“…In the second part of our study we showed a significant change in the locomotor activity in rats in the hole-board after LHb lesion when compared to sham-lesioned rats, as previously observed in many other studies (Nielson and McIver, 1966 ; Lecourtier et al, 2008 ; Gifuni et al, 2012 ; Wang et al, 2013 ; Jean-Richard Dit Bressel and McNally, 2014 ) validating the manipulation within the current study. This locomotor effect is likely due to the strong inhibitory control over midbrain DA neurons exerted by the LHb (Matsumoto and Hikosaka, 2007 ).…”

Section: Discussionsupporting

confidence: 91%

Acute nicotine induces anxiety and disrupts temporal pattern organization of rat exploratory behavior in hole-board: a potential role for the lateral habenula

Casarrubea

Davies

Faulisi

et al. 2015

Front. Cell. Neurosci.

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Nicotine is one of the most addictive drugs of abuse. Tobacco smoking is a major cause of many health problems, and is the first preventable cause of death worldwide. Several findings show that nicotine exerts significant aversive as well as the well-known rewarding motivational effects. Less certain is the anatomical substrate that mediates or enables nicotine aversion. Here, we show that acute nicotine induces anxiogenic-like effects in rats at the doses investigated (0.1, 0.5, and 1.0 mg/kg, i.p.), as measured by the hole-board apparatus and manifested in behaviors such as decreased rearing and head-dipping and increased grooming. No changes in locomotor behavior were observed at any of the nicotine doses given. T-pattern analysis of the behavioral outcomes revealed a drastic reduction and disruption of complex behavioral patterns induced by all three nicotine doses, with the maximum effect for 1 mg/kg. Lesion of the lateral habenula (LHb) induced hyperlocomotion and, strikingly, reversed the nicotine-induced anxiety obtained at 1 mg/kg to an anxiolytic-like effect, as shown by T-pattern analysis. We suggest that the LHb is critically involved in emotional behavior states and in nicotine-induced anxiety, most likely through modulation of monoaminergic nuclei.

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Section: Discussionsupporting

confidence: 91%

Acute nicotine induces anxiety and disrupts temporal pattern organization of rat exploratory behavior in hole-board: a potential role for the lateral habenula

Casarrubea

Davies

Faulisi

et al. 2015

Front. Cell. Neurosci.

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“…Optogenetic stimulation of the LHb → RMTg pathway negatively reinforces nose-poking and suppresses acquisition of a reinforced response [ 152 ]. However, these studies did not isolate punishment and a variety of approaches to preventing LHb activity do not affect punishment suppression in rats [ 165 ]. That said, the LHb appears to play important roles in active avoidance [ 159 ] and risky decision-making [ 166 ].…”

Section: Brain Mechanisms Of Punishmentmentioning

confidence: 99%

Behavioral and neurobiological mechanisms of punishment: implications for psychiatric disorders

Jean-Richard-dit-Bressel

Killcross

McNally

2018

Neuropsychopharmacol

Self Cite

118

100

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Punishment involves learning about the relationship between behavior and its adverse consequences. Punishment is fundamental to reinforcement learning, decision-making and choice, and is disrupted in psychiatric disorders such as addiction, depression, and psychopathy. However, little is known about the brain mechanisms of punishment and much of what is known is derived from study of superficially similar, but fundamentally distinct, forms of aversive learning such as fear conditioning and avoidance learning. Here we outline the unique conditions that support punishment, the contents of its learning, and its behavioral consequences. We consider evidence implicating GABA and monoamine neurotransmitter systems, as well as corticostriatal, amygdala, and dopamine circuits in punishment. We show how maladaptive punishment processes are implicated in addictions, impulse control disorders, psychopathy, anxiety, and depression and argue that a better understanding of the cellular, circuit, and cognitive mechanisms of punishment will make important contributions to next generation therapeutic approaches.

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“…The role of the lateral division of the habenular complex (LHb) in regulating dopaminergic activity in the VTA via the rostromedial tegmental nucleus has been established, and represents an important mechanism by which aversion and addiction are modulated (Barrot et al 2012, Sanchez-Catalan et al 2016, Jean-Richard Dit Bressel & McNally 2014, Quina et al 2015). Both the LHb and MHb send dense efferent projections through the fasciculus retroflexus, and anatomical studies suggest that projections emerging from the MHb course through the core and those from the LHb through the sheath of this dense fiber bundle (Bianco & Wilson 2009).…”

Section: Nicotine and Psychomotor Stimulantsmentioning

confidence: 99%

The medial habenula and interpeduncular nucleus circuitry is critical in addiction, anxiety, and mood regulation

McLaughlin

Dani

Biasi

2017

Journal of Neurochemistry

156

106

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Abstinence from chronic use of addictive drugs triggers an aversive withdrawal syndrome that compels relapse and deters abstinence. Many features of this syndrome are common across multiple drugs, involving both affective and physical symptoms. Some of the network signaling underlying withdrawal symptoms overlaps with activity that is associated with aversive mood states, including anxiety and depression. Given these shared features, it is not surprising that a particular circuit, the dorsal diencephalic conduction system, and the medial habenula (MHb) and interpeduncular nucleus (IPN), in particular, have been identified as critical to the emergence of aversive states that arise both as a result and, independently, of drug addiction. As the features of this circuit continue to be characterized, the MHb-IPN axis is emerging as a viable target for therapeutics to aid in the treatment of addiction to multiple drugs of abuse as well as moodassociated disorders.

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The Role of the Lateral Habenula in Punishment

Cited by 21 publications

References 33 publications

Acute nicotine induces anxiety and disrupts temporal pattern organization of rat exploratory behavior in hole-board: a potential role for the lateral habenula

Acute nicotine induces anxiety and disrupts temporal pattern organization of rat exploratory behavior in hole-board: a potential role for the lateral habenula

Behavioral and neurobiological mechanisms of punishment: implications for psychiatric disorders

The medial habenula and interpeduncular nucleus circuitry is critical in addiction, anxiety, and mood regulation

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