Stimulating GABAergic Neurons in the Nucleus Accumbens Core Alters the Trigeminal Neuropathic Pain Responses in a Rat Model of Infraorbital Nerve Injury

The nucleus accumbens core (NAcc) is an important component of brain reward circuitry, but studies have revealed its involvement in pain circuitry also. However, its effect on trigeminal neuralgia (TN) and the mechanism underlying it are yet to be fully understood. Therefore, this study aimed to examine the outcomes of optogenetic stimulation of NAcc GABAergic neurons in an animal model of TN. Animals were allocated into TN, sham, and control groups. TN was generated by infraorbital nerve constriction and the optogenetic virus was injected into the NAcc. In vivo extracellular recordings were acquired from the ventral posteromedial nucleus of the thalamus. Alterations of behavioral responses during stimulation “ON” and “OFF” conditions were evaluated. In vivo microdialysis was performed in the NAcc of TN and sham animals. During optogenetic stimulation, electrophysiological recordings revealed a reduction of both tonic and burst firing activity in TN animals, and significantly improved behavioral responses were observed as well. Microdialysis coupled with liquid chromatography/tandem mass spectrometry analysis revealed significant alterations in extracellular concentration levels of GABA, glutamate, acetylcholine, dopamine, and citrulline in NAcc upon optic stimulation. In fine, our results suggested that NAcc stimulation could modulate the transmission of trigeminal pain signals in the TN animal model.

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A subset of nucleus accumbens neurons receiving dense and functional prelimbic cortical input are required for cocaine seeking

10.1101/2021.09.03.458762 ◽

2021 ◽

Author(s):

Benjamin M. Siemsen ◽

Sarah M. Barry ◽

Kelsey Vollmer ◽

Lisa M. Green ◽

Ashley G. Brock ◽

...

Keyword(s):

Nucleus Accumbens ◽

Glutamate Release ◽

Sprague Dawley ◽

Self Administration ◽

Nucleus Accumbens Core ◽

Cortical Input ◽

Cortical Projections ◽

Cocaine Seeking ◽

Accumbens Core

AbstractBackgroundPrelimbic cortical projections to the nucleus accumbens core are critical for cue-induced cocaine seeking, but the identity of the accumbens neuron(s) targeted by this projection, and the transient neuroadaptations contributing to relapse within these cells, remain unknown.MethodsMale Sprague-Dawley rats underwent cocaine or sucrose self-administration, extinction, and cue-induced reinstatement. Pathway-specific chemogenetics, patch-clamp electrophysiology, in vivo electrochemistry, and high-resolution confocal microscopy were used to identify and characterize a small population of nucleus accumbens core neurons that receive dense prelimbic cortical input to determine their role in regulating cue-induced cocaine and natural reward seeking.ResultsChemogenetic inhibition of prelimbic cortical projections to the nucleus accumbens core suppressed cue-induced cocaine relapse and normalized real-time cue-evoked increases in accumbens glutamate release to that of sucrose seeking animals. Furthermore, chemogenetic inhibition of the population of nucleus accumbens core neurons receiving the densest prelimbic cortical input suppressed cocaine, but not sucrose seeking. These neurons also underwent morphological plasticity during the peak of cocaine seeking in the form of dendritic spine expansion and increased ensheathment by astroglial processes at large spines.ConclusionsWe identified and characterized a unique subpopulation of nucleus accumbens neurons that receive dense prelimbic cortical input. The functional specificity of this subpopulation is underscored by their ability to mediate cue-induced cocaine relapse, but not sucrose seeking. This subset of cells represents a novel target for addiction therapeutics revealed by anterograde targeting to interrogate functional circuits imbedded within a known network.

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Chronic morphine induces long-lasting changes in acetylcholine release in rat nucleus accumbens core and shell: an in vivo microdialysis study

Psychopharmacology ◽

10.1007/s002130050866 ◽

1999 ◽

Vol 142 (1) ◽

pp. 85-94 ◽

Cited By ~ 43

Author(s):

Magdaléna Fiserová ◽

Silvana Consolo ◽

Miloslav Krsiak

Keyword(s):

Nucleus Accumbens ◽

Acetylcholine Release ◽

In Vivo Microdialysis ◽

Nucleus Accumbens Core ◽

Chronic Morphine ◽

Rat Nucleus Accumbens ◽

Microdialysis Study ◽

Accumbens Core

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Optogenetic activation of basolateral amygdala projections to nucleus accumbens core promotes cue-induced expectation of reward but not instrumental pursuit of cues

10.1101/2021.10.20.465037 ◽

2021 ◽

Author(s):

Alice Servonnet ◽

Pierre-Paul Rompré ◽

Anne-Noël Samaha

Keyword(s):

Nucleus Accumbens ◽

Basolateral Amygdala ◽

Male Rats ◽

Water Delivery ◽

Nucleus Accumbens Core ◽

Approach Behavior ◽

Optogenetic Stimulation ◽

Conditioned Approach ◽

Stimulation Of ◽

Accumbens Core

Reward-associated conditioned stimuli (CS) can acquire predictive value, evoking conditioned approach behaviors that prepare animals to engage with forthcoming rewards. Such CS can also acquire conditioned reinforcing value, becoming attractive and pursued. Through their predictive and conditioned reinforcing properties, CS can promote adaptive (e.g., locating food) but also maladaptive responses (e.g., drug use). Basolateral amygdala neurons projecting to the nucleus accumbens core (BLA→NAc core neurons) mediate the response to appetitive CS, but the extent to which this involves effects on the predictive and/or conditioned reinforcing properties of CS is unclear. Thus, we examined the effects of optogenetic stimulation of BLA→NAc core neurons on conditioned approach behavior and on the instrumental pursuit of a CS, the latter a measure of conditioned reinforcement. Water-restricted, adult male rats learned that a light-tone compound cue (CS) predicts water delivery. Pairing optogenetic stimulation of BLA→NAc core neurons with CS presentation potentiated conditioned approach behavior, and did so even under extinction conditions, when water was omitted. This suggests that BLA→NAc core neurons promote cue-induced expectation of rewards. Rats also received instrumental conditioning sessions during which they could lever press for CS presentations, without water delivery. Optogenetic stimulation of BLA→NAc core neurons either during these instrumental test sessions or during prior CS-water conditioning did not influence lever responding for the CS. This suggests that BLA→NAc core neurons do not influence the conditioned reinforcing effects of CS. We conclude that BLA→NAc core neurons promote cue-induced control over behavior by increasing cue-triggered anticipation of rewards, without influencing cue 'wanting'.

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