Learning processes in relapse to alcohol use: lessons from animal models

Valyear, Milan D; LeCocq, Mandy Rita; Brown, Alexa; Villaruel, Franz R.; Segal, Diana; Chaudhri, Nadia

doi:10.1007/s00213-022-06254-x

Cited by 5 publications

(5 citation statements)

References 254 publications

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“…Occasion setting is a process that captures the control of behavioral responding by contexts (Grahame et al, 1990; Holland, 1992; Holland and Bouton, 1999; Bouton et al, 2006; Fraser and Holland, 2019; Valyear et al, 2023). Despite evidence that dopamine neurons and their striatal targets are essential for the contextual-control of reward-seeking it has been difficult to disentangle the contribution of dopamine neuron activity to encoding contextual control or merely the generation of reward-seeking by cues.…”

Section: Discussionmentioning

confidence: 99%

“…This is because traditional context-based approaches (e.g. renewal and reinstatement) are not amenable to separating these processes because the use of a large, multidimensional, and temporally diffuse setting prevents experimenter control over its actions (Crombag et al, 2008;Chaudhri et al, 2010;Floresco, 2015;Valyear et al, 2020Valyear et al, , 2023. By reducing a "context" to a brief and discrete event, an occasion setter, we were able to resolve that dopamine neuron activity during the presentation of this context-like occasion setting cue was necessary for that cue to then gate reward-seeking to an ambiguous conditioned stimulus.…”

Section: Discussionmentioning

confidence: 99%

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Contexts facilitate dynamic value encoding in the mesolimbic dopamine system

Fraser,

Collins,

Wolff

et al. 2023

Preprint

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Adaptive behavior in a dynamic environment often requires rapid revaluation of stimuli that deviates from well-learned associations. The divergence between stable value-encoding and appropriate behavioral output remains a critical test to theories of dopamine’s function in learning, motivation, and motor control. Yet how dopamine neurons are involved in the revaluation of cues when the world changes to alter our behavior remains unclear. Here we make use of pharmacology, in vivo electrophysiology, fiber photometry, and optogenetics to resolve the contributions of the mesolimbic dopamine system to the dynamic reorganization of reward-seeking. Male and female rats were trained to discriminate when a conditioned stimulus would be followed by sucrose reward by exploiting the prior, non-overlapping presentation of a separate discrete cue - an occasion setter. Only when the occasion setter’s presentation preceded the conditioned stimulus did the conditioned stimulus predict sucrose delivery. As a result, in this task we were able to dissociate the average value of the conditioned stimulus from its immediate expected value on a trial-to-trial basis. Both the activity of ventral tegmental area dopamine neurons and dopamine signaling in the nucleus accumbens were essential for rats to successfully update behavioral responding in response to the occasion setter. Moreover, dopamine release in the nucleus accumbens following the conditioned stimulus only occurred when the occasion setter indicated it would predict reward. Downstream of dopamine release, we found that single neurons in the nucleus accumbens dynamically tracked the value of the conditioned stimulus. Together these results reveal a novel mechanism within the mesolimbic dopamine system for the rapid revaluation of motivation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Contexts facilitate dynamic value encoding in the mesolimbic dopamine system

Fraser,

Collins,

Wolff

et al. 2023

Preprint

View full text Add to dashboard Cite

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“…So‐called cue reactivity is a core component of psychopathologies that contend with relapse as a barrier to recovery, such as binge eating and alcohol use disorder. Reactivity to cues and contexts associated with palatable foods or alcohol are enduring relapse triggers (Gearhardt & DiFeliceantonio, 2022; Valyear et al, 2022), even in people that have undergone surgical treatment interventions (Budak & Thomas, 2009; Ho et al, 2018). Uncovering the neural circuits that subserve the capacity for cues and contexts to encourage the pursuit of rewards, like palatable foods and alcohol, informs efforts to understand and prevent relapse.…”

Section: Figurementioning

confidence: 99%

A new circuit underlying the renewal of appetitive Pavlovian responses: Commentary on Brown and Chaudhri (2022)

Valyear

Britt

2023

Eur J of Neuroscience

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“…This endeavour led to the proliferation of sophisticated conditioning procedures and their combination with contemporary neuroscience tools in preclinical research. Consequently, considerable work demonstrates the necessity of glutamatergic and dopaminergic signalling within the nucleus accumbens (NAc) shell for responding to discrete alcohol cues and contexts (Kalivas et al, 2006; Valyear et al, 2023). There is, however, a paucity in understanding the neural substrates that cause , and are thus sufficient to elevate, responding to discrete alcohol cues and contexts.…”

Section: Introductionmentioning

confidence: 99%

Augmenting glutamatergic, but not dopaminergic, activity in the nucleus accumbens shell disrupts responding to a discrete alcohol cue in an alcohol context

Valyear,

Brown,

Deyab

et al. 2024

Eur J of Neuroscience

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Discrete alcohol cues and contexts are relapse triggers for people with alcohol use disorder exerting particularly powerful control over behaviour when they co‐occur. Here, we investigated the neural substrates subserving the capacity for alcohol‐associated contexts to elevate responding to an alcohol‐predictive conditioned stimulus (CS). Specifically, rats were trained in a distinct ‘alcohol context’ to respond by entering a fluid port during a discrete auditory CS that predicted the delivery of alcohol and were familiarized with a ‘neutral context’ wherein alcohol was never available. When conditioned CS responding was tested by presenting the CS without alcohol, we found that augmenting glutamatergic activity in the nucleus accumbens (NAc) shell by microinfusing α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) reduced responding to an alcohol CS in an alcohol, but not neutral, context. Further, AMPA microinfusion robustly affected behaviour, attenuating the number, duration and latency of CS responses selectively in the alcohol context. Although dopaminergic inputs to the NAc shell were previously shown to be necessary for CS responding in an alcohol context, here, chemogenetic excitation of ventral tegmental area (VTA) dopamine neurons and their inputs to the NAc shell did not affect CS responding. Critically, chemogenetic excitation of VTA dopamine neurons affected feeding behaviour and elevated c‐fos immunoreactivity in the VTA and NAc shell, validating the chemogenetic approach. These findings enrich our understanding of the substrates underlying Pavlovian responding for alcohol and reveal that the capacity for contexts to modulate responding to discrete alcohol cues is delicately underpinned by the NAc shell.

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Learning processes in relapse to alcohol use: lessons from animal models

Cited by 5 publications

References 254 publications

Contexts facilitate dynamic value encoding in the mesolimbic dopamine system

Contexts facilitate dynamic value encoding in the mesolimbic dopamine system

A new circuit underlying the renewal of appetitive Pavlovian responses: Commentary on Brown and Chaudhri (2022)

Augmenting glutamatergic, but not dopaminergic, activity in the nucleus accumbens shell disrupts responding to a discrete alcohol cue in an alcohol context

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