scholarly journals Nucleus accumbens D1-receptors regulate and focus transitions to reward-seeking action

2021 ◽  
Author(s):  
Laura L Grima ◽  
Marios C Panayi ◽  
Oliver Harmson ◽  
Emilie Syed ◽  
Sanjay G Manohar ◽  
...  

While it is well established that dopamine transmission is integral in mediating the influence of reward expectations on reward-seeking actions, the precise causal role of dopamine transmission in moment-to-moment cue-driven behavioural control remains contentious. This is a particular issue in situations where it is necessary to refrain from responding to achieve a beneficial outcome. To examine this, we manipulated dopamine transmission pharmacologically as rats performed a Go/No-Go task that required them to either make or withhold action to gain either a small or large reward. Stimulation of D1Rs, both globally and locally in the nucleus accumbens core (NAcC) region consistently disrupted No-Go performance, potentiating inappropriate responses that clustered strongly just after cue presentation. D1R blockade did not, however, improve rats' ability to withhold responses, but instead primarily disrupted performance on Go trials. While global D1R blockade caused a general reduction of invigoration of reward seeking actions, intra-NAcC administration of the D1R antagonist by contrast increased the likelihood that Go trial performance was in an "unfocused" state. Such a state was characterised, both on and off drug, by a reduction in the precision and speed of responding even though the appropriate action sequence was often executed. These findings suggests that the balance of activity at NAcC D1Rs plays a key role in enabling the rapid activation of a focused, reward-seeking state to enable animals to efficiently and accurately achieve their goal.

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Briac Halbout ◽  
Andrew T Marshall ◽  
Ali Azimi ◽  
Mimi Liljeholm ◽  
Stephen V Mahler ◽  
...  

Efficient foraging requires an ability to coordinate discrete reward-seeking and reward-retrieval behaviors. We used pathway-specific chemogenetic inhibition to investigate how rats’ mesolimbic and mesocortical dopamine circuits contribute to the expression and modulation of reward seeking and retrieval. Inhibiting ventral tegmental area dopamine neurons disrupted the tendency for reward-paired cues to motivate reward seeking, but spared their ability to increase attempts to retrieve reward. Similar effects were produced by inhibiting dopamine inputs to nucleus accumbens, but not medial prefrontal cortex. Inhibiting dopamine neurons spared the suppressive effect of reward devaluation on reward seeking, an assay of goal-directed behavior. Attempts to retrieve reward persisted after devaluation, indicating they were habitually performed as part of a fixed action sequence. Our findings show that complete bouts of reward seeking and retrieval are behaviorally and neurally dissociable from bouts of reward seeking without retrieval. This dichotomy may prove useful for uncovering mechanisms of maladaptive behavior.


2020 ◽  
Author(s):  
Allison R. Bechard ◽  
Carly N. Logan ◽  
Javier Mesa ◽  
Yasmin Padovan‐Hernandez ◽  
Harrison Blount ◽  
...  

2014 ◽  
Vol 76 (10) ◽  
pp. 810-815 ◽  
Author(s):  
Susan E. Doyle ◽  
Carolina Ramôa ◽  
Garrett Garber ◽  
Joshua Newman ◽  
Zeeshan Toor ◽  
...  

2019 ◽  
Author(s):  
Anne L. Collins ◽  
Tara J. Aitken ◽  
I-Wen Huang ◽  
Christine Shieh ◽  
Venuz Y. Greenfield ◽  
...  

ABSTRACTBackgroundEnvironmental reward-predictive stimuli provide a major source of motivation for adaptive reward pursuit behavior. This cue-motivated behavior is known to be mediated by the nucleus accumbens core (NAc). The cholinergic interneurons in the NAc are tonically active and densely arborized and, thus, well-suited to modulate NAc function. But their causal contribution to adaptive behavior remains unknown. Here we investigated the function of NAc cholinergic interneurons in cue-motivated behavior.MethodsTo do this, we used chemogenetics, optogenetics, pharmacology, and a translationally analogous Pavlovian-to-instrumental transfer behavioral task designed to assess the motivating influence of a reward-predictive cue over reward-seeking actions in male and female rats.ResultsThe data show that NAc cholinergic interneuron activity is necessary and sufficient to oppose the motivating influence of appetitive cues. Chemogenetic inhibition of NAc cholinergic interneurons augmented cue-motivated behavior. Optical stimulation of acetylcholine release from NAc cholinergic interneurons prevented cues from invigorating reward-seeking behavior, an effect that was mediated by activation of β2-containing nicotinic acetylcholine receptors.ConclusionsThus, NAc cholinergic interneurons provide a critical regulatory influence over adaptive cue-motivated behavior and, therefore, are a potential therapeutic target for the maladaptive cue-motivated behavior that marks many psychiatric conditions, including addiction and depression.


1986 ◽  
Vol 251 (2) ◽  
pp. G270-G274 ◽  
Author(s):  
K. Tabata ◽  
L. R. Johnson

The purpose of this study was to examine the role of ornithine decarboxylase (ODC) in the stimulation of the growth of gastrointestinal mucosa following feeding. Rats were divided into five groups: 1) fasted for 2 days, 2) fasted for 2 days and refed for 2 days, 3) fasted for 2 days and refed with the addition of 5% difluoromethylornithine (DFMO) to the drinking water, 4) normally fed, and 5) normally fed plus 5% DFMO in the drinking water. In general the results show a significant dissociation between ODC activity and growth of gastrointestinal mucosa in response to feeding. In the gastric mucosa, growth was inhibited by fasting and DFMO and stimulated by feeding, but there were no significant changes in ODC activity in any of the five groups. In the ileum ODC activity increased dramatically in refed rats and was essentially eliminated in rats fed DFMO. DFMO, however, had no effect on mucosal growth in fed rats and only prevented part of the trophic response to refeeding. The results in the colon were much the same as in the ileum, except that DFMO prevented even less of the trophic response to refeeding, despite total inhibition of ODC. These data suggest that polyamines necessary for growth of gastrointestinal mucosa following feeding are not supplied by the rapid activation of mucosal ornithine decarboxylase.


IBRO Reports ◽  
2019 ◽  
Vol 6 ◽  
pp. S347
Author(s):  
Elina Kc ◽  
Hyeong Cheol Moon ◽  
Sang Hwan Hyun ◽  
Young Seok Park

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