Amygdala mu‐opioid receptors mediate the motivating influence of cue‐triggered reward expectations

Lichtenberg, Nina T.; Wassum, Kate M.

doi:10.1111/ejn.13477

Cited by 23 publications

(23 citation statements)

References 36 publications

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“…We also found the BLA to be necessary, specifically at the time of stimulus-reward pairing, to encode the detailed stimulus-outcome memories. This is consistent with evidence that either pre-or post-training BLA lesion or pre-test inactivation disrupts appetitive conditional behaviors that rely on a sensory-specific, stimulusoutcome memory in rodents (Blundell et al, 2001;Corbit & Balleine, 2005;Derman et al, 2020;Hatfield et al, 1996;Lichtenberg et al, 2017;Lichtenberg & Wassum, 2016;Malvaez et al, 2015;Morse et al, 2020;Ostlund & Balleine, 2008) and in primates (Murray & Izquierdo, 2007;Málková et al, 1997). Leveraging the temporal resolution of optogenetics, we demonstrated that the BLA mediates the encoding of such memories.…”

Section: Discussionsupporting

confidence: 91%

“…A 3-watt, 24-volt house light mounted on the top of the back wall opposite the food-delivery port provided illumination and a fan mounted to the outer chamber provided ventilation and external noise reduction. Behavioral procedures were similar to that we have described previously (Lichtenberg et al, 2017;Lichtenberg & Wassum, 2016;Malvaez et al, 2015) Magazine conditioning. Rats first received one day of training to learn where to receive the sucrose and food pellet rewards.…”

Section: Behavioral Proceduresmentioning

confidence: 99%

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A bidirectional corticoamygdala circuit for the encoding and retrieval of detailed reward memories

Sias¹,

Morse²,

Wang³

et al. 2021

Preprint

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Adaptive reward-related decision making often requires accurate and detailed representation of potential available rewards. Environmental reward-predictive stimuli can facilitate these representations, allowing one to infer which specific rewards might be available and choose accordingly. This process relies on encoded relationships between the cues and the sensory-specific details of the reward they predict. Here we interrogated the function of the basolateral amygdala (BLA) and its interaction with the lateral orbitofrontal cortex (lOFC) in the ability to learn such stimulus-outcome associations and use these memories to guide decision making. Using optical recording and inhibition approaches, Pavlovian cue-reward conditioning, and an outcome-selective Pavlovian-to-instrumental transfer (PIT) test in male rats, we found that the BLA is robustly activated at the time of stimulus-outcome learning and that this activity is necessary for sensory-specific stimulus-outcome memories to be encoded, so that they can subsequently influence reward choices. Direct input from the lOFC was found to support the BLA in this function. Based on prior work, activity in BLA projections back to the lOFC was known to support the use of stimulus-outcome memories to influence decision making. By multiplexing optogenetic and chemogenetic inhibition to perform a serial circuit disconnection, we found that activity in lOFC→BLA projections regulates the encoding of the same components of the stimulus-outcome memory that are later used to allow cues to guide choice via activity in BLA→lOFC projections. Thus, the lOFC→BLA→lOFC circuit regulates the encoding (lOFC→BLA) and subsequent use (BLA→lOFC) of the stimulus-dependent, sensory-specific reward memories that are critical for adaptive, appetitive decision making.

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Section: Discussionsupporting

confidence: 91%

Section: Behavioral Proceduresmentioning

confidence: 99%

A bidirectional corticoamygdala circuit for the encoding and retrieval of detailed reward memories

Sias¹,

Morse²,

Wang³

et al. 2021

Preprint

Self Cite

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“…Overall, cue-controlled cocaine and heroin seeking both involve dopamine, GABA(B) (Di Ciano & Everitt, 2003), and l-opioid receptor-dependent mechanisms (Giuliano et al, 2013). The rather counter-intuitive reliance of cue-controlled drug seeking on opioidergic mechanisms may be related to their involvement in the basolateral amygdala in mediating the motivational control of CSs over instrumental performance (Lichtenberg & Wassum, 2017).…”

Section: Discussionmentioning

confidence: 99%

Heroin seeking becomes dependent on dorsal striatal dopaminergic mechanisms and can be decreased by N‐acetylcysteine

Hodebourg

Murray

Fouyssac

et al. 2018

Eur J of Neuroscience

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The alarming increase in heroin overdoses in the USA is a reminder of the need for efficacious and novel treatments for opiate addiction. This may reflect the relatively poor understanding of the neural basis of heroin, as compared to cocaine, seeking behaviour. While cocaine reinforcement depends on the mesolimbic system, well-established cocaine seeking is dependent on dorsolateral striatum (aDLS) dopamine-dependent mechanisms which are disrupted by N-acetylcysteine, through normalisation of corticostriatal glutamate homeostasis. However, it is unknown whether a functional recruitment of aDLS dopamine-dependent control over instrumental responding also occurs for heroin seeking, even though heroin reinforcement does not depend on the mesolimbic dopamine system. Lister Hooded rats acquired heroin self-administration and were subsequently trained to seek heroin daily over prolonged periods of time under the control of drug-paired cues, as measured under a second-order schedule of reinforcement. At different stages of training, that is, early on and when heroin seeking behaviour was well established, we measured the sensitivity of drug-seeking responses to either bilateral aDLS infusions of the dopamine receptor antagonist α-flupenthixol (5, 10 and 15 μg/side) or systemic administration of N-acetylcysteine (30, 60 and 90 mg/kg). The results demonstrate that control over heroin seeking behaviour devolves to aDLS dopamine-dependent mechanisms after extended training. Further aDLS-dependent well-established, cue-controlled heroin seeking was disrupted by N-acetylcysteine. Comparison with previous data on cocaine suggests that the development of drug seeking habits and the alteration of corticostriatal glutamate homeostasis, which is restored by N-acetylcysteine, are quantitatively similar between heroin and cocaine.

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“…An answer to this puzzle comes by noting that MOR promotes innate responses to cues predicting reward. For example, BLA MORs facilitate vigorous approach to predictive food cues [Lichtenberg and Wassum, 2017]. Cues are learned by conditioning, so are part of the innate+ system, which extends the innate system.…”

Section: Consume: Beta-endorphin (Bend)mentioning

confidence: 99%

The Brain, Explained: A Comprehensive Theory of Brain Function

Rappoport¹

2018

Preprint

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Understanding brain function is one of the most important problems in human history. At present, there is no concrete theory for how the brain works. Here, a theory is presented that provides a detailed mechanistic biological account of the brain's capacities, including motor control, functional states, language, and thinking. Brain function is managed by a well-defined r e sponse ( R ) p r ocess t h at i s generally similar to the process underlying the immune system. The R process is strongly reflected in the brain's anatomy, physiology, and external i n teractions. Different R process stages are supported by distinct excitatory networks located in different cortical layers, hippocampal fields, and bagal ganglia paths, by distinct coordination networks comprised of GABAergic interneurons, and by distinct molecular agents. The roles of norepinephrine, serotonin, dopamine and acetylcholine is to promote the alert, planning, goal-setting and execution R process modes, respectively. Opioids and oxytocin promote termination by success, failure, fight o r r un, w hile g lucocorticoids and cannabinoids suppress acute responses to protect cells. The R process has two instances occurring at different time scales. The millisecondscale Quax process implements the execution of hierarchical sequences of movements and thoughts, in which the selection of the next action is determined via interaction between top-down predictions and sensory inputs. The slower Need process controls the satisfaction of internal and external needs. The theory differs from the existing standard accounts in many of the major topics (e.g., the basal ganglia, dopamine, language), and shows how cognition results from biological processes.

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Amygdala mu‐opioid receptors mediate the motivating influence of cue‐triggered reward expectations

Cited by 23 publications

References 36 publications

A bidirectional corticoamygdala circuit for the encoding and retrieval of detailed reward memories

A bidirectional corticoamygdala circuit for the encoding and retrieval of detailed reward memories

Heroin seeking becomes dependent on dorsal striatal dopaminergic mechanisms and can be decreased by N‐acetylcysteine

The Brain, Explained: A Comprehensive Theory of Brain Function

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