Relief learning requires a coincident activation of dopamine D1 and NMDA receptors within the nucleus accumbens

Acosta, Jorge R. Bergado; Kahl, Evelyn; Kogias, Georgios; Uzuneser, Taygun C.; Fendt, Markus

doi:10.1016/j.neuropharm.2016.11.022

Cited by 13 publications

(18 citation statements)

References 53 publications

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“…Furthermore, chemogenetic inactivation of the pmVTA-AcbSh projection as well as local blockade of dopamine D2/3 receptors within the AcbSh inhibited the acquisition of conditioned relief. Notably, we previously published an important role of accumbal dopamine D1 receptors in the acquisition and expression of conditioned relief [28]. Taken together, these findings indicate that the dopaminergic pmVTA-AcbSh projection and accumbal dopamine receptors are crucially involved in relief learning.…”

Section: Introductionmentioning

confidence: 53%

“…Experiment 2. Ten days after injections of vehicle or 6-OHDA, rats were subjected to a relief-conditioning procedure as previously described [28]. After 5 min acclimation time, 15 pairings of an electric stimulus with the light stimulus were presented (mean ITI: 2 min, range: 1.5-2.5 min).…”

Section: Startle Apparatus and Stimulus Parametermentioning

confidence: 99%

“…The scientific question of the present study is based on findings that the nucleus accumbens is crucially involved in relief learning [23,24,28,29,47] and that some neurons of the pmVTA are activated by the offset of an aversive event [32], i.e. in the moment of relief.…”

Section: Role Of the Pmvta-acbsh Projection In Relief Learningmentioning

confidence: 99%

“…We further asked whether a blockade of dopamine receptors within the AcbSh would have similar effects. We recently demonstrated that accumbal injections of the selective dopamine D1 receptor antagonist SCH23390 inhibit the acquisition and expression of conditioned relief [28]. However, an involvement of other dopamine receptor subtypes was not investigated so far.…”

Section: Role Of the Pmvta-acbsh Projection In Relief Learningmentioning

confidence: 99%

“…Regarding relief learning, there is already a good deal of information available [3]: Human imaging studies found the nucleus accumbens to be activated during both acute relief [21,22] and learned relief [23,24]. Studies in laboratory rodents confirmed the crucial role of the nucleus accumbens in relief learning [25,26] and showed that relief learning is mediated and modulated by glutamatergic and dopaminergic transmission within the nucleus accumbens [26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

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Role of the mesolimbic dopamine system in relief learning

Mayer

Kahl

Uzuneser

et al. 2018

Neuropsychopharmacol

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The relief from an aversive event is rewarding. Since organisms are able to learn which environmental cues can cease an aversive event, relief learning helps to better cope with future aversive events. Literature data suggest that relief learning is affected in various psychopathological conditions, such as anxiety disorders. Here, we investigated the role of the mesolimbic dopamine system in relief learning. Using a relief learning procedure in Sprague Dawley rats, we applied a combination of behavioral experiments with anatomical tracing, c-Fos immunohistochemistry, and local chemogenetic and pharmacological interventions to broadly characterize the role of the mesolimbic dopamine system. The present study shows that a specific part of the mesolimbic dopamine system, the projection from the posterior medial ventral tegmental area (pmVTA) to the nucleus accumbens shell (AcbSh), is activated by aversive electric stimuli. 6-OHDA lesions of the pmVTA blocked relief learning but fear learning and safety learning were not affected. Chemogenetic silencing of the pmVTA-AcbSh projection using the DREADD approach, as well as intra-AcbSh injections of the dopamine D2/3 receptor antagonist raclopride inhibited relief learning. Taken together, the present data demonstrate that the dopaminergic pmVTA-AcbSh projection is critical for relief learning but not for similar learning phenomena. This novel finding may have clinical implications since the processing of signals predicting relief and safety is often impaired in patients suffering from anxiety disorders. Furthermore, it may help to better understand psychological conditions like non-suicidal self-injury, which are associated with pain offset relief.

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Section: Introductionmentioning

confidence: 53%

Section: Startle Apparatus and Stimulus Parametermentioning

confidence: 99%

Section: Role Of the Pmvta-acbsh Projection In Relief Learningmentioning

confidence: 99%

Section: Role Of the Pmvta-acbsh Projection In Relief Learningmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Role of the mesolimbic dopamine system in relief learning

Mayer

Kahl

Uzuneser

et al. 2018

Neuropsychopharmacol

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Foot shock facilitates reward seeking in an experience-dependent manner

Strickland

Dileo

Moaddab

et al. 2021

Behavioural Brain Research

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Animals organize reward seeking around aversive events. An abundance of research shows that foot shock, as well as a shock-associated cue, can elicit freezing and suppress reward seeking. Yet, there is evidence that experience can flip the effect of foot shock to facilitate reward seeking. Here we examine cue suppression, foot shock suppression and foot shock facilitation of reward seeking in a single behavioural setting. Male Long Evans rats received fear discrimination consisting of danger, uncertainty and safety cues. Discrimination took place over a baseline of rewarded nose poking. With limited experience, all cues and foot shock strongly suppressed reward seeking. With continued experience, suppression became specific to shock-associated cues and foot shock facilitated reward seeking. Our results provide a means of assessing positive properties of foot shock, and may provide insight into maladaptive behavior around aversive events.

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