scholarly journals Alcohol consumption increases basal extracellular glutamate in the nucleus accumbens core of Sprague-Dawley rats without increasing spontaneous glutamate release

2016 ◽  
Vol 44 (2) ◽  
pp. 1896-1905 ◽  
Author(s):  
Dipanwita Pati ◽  
Kyle Kelly ◽  
Bethany Stennett ◽  
Charles J. Frazier ◽  
Lori A. Knackstedt
Keyword(s):  
Nucleus Accumbens ◽  
Alcohol Consumption ◽  
Glutamate Release ◽  
Sprague Dawley ◽  
Nucleus Accumbens Core ◽  
Extracellular Glutamate ◽  
Sprague Dawley Rats ◽  
Accumbens Core

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

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.

scholarly journals Sensitization of Rapid Dopamine Signaling in the Nucleus Accumbens Core and Shell After Repeated Cocaine in Rats

2010 ◽  
Vol 104 (2) ◽  
pp. 922-931 ◽  
Author(s):  
Nii A. Addy ◽  
David P. Daberkow ◽  
Jeremy N. Ford ◽  
Paul A. Garris ◽  
R. Mark Wightman
Keyword(s):  
Nucleus Accumbens ◽  
Dopamine Release ◽  
Cocaine Exposure ◽  
Sprague Dawley ◽  
Nucleus Accumbens Core ◽  
Fast Scan Cyclic Voltammetry ◽  
Uptake Inhibition ◽  
Sprague Dawley Rats ◽  
Dopamine Signaling

Repeated cocaine exposure and withdrawal leads to long-term changes, including behavioral and dopamine sensitization to an acute cocaine challenge, that are most pronounced after long withdrawal periods. However, the changes in dopamine neurotransmission after short withdrawal periods are less well defined. To study dopamine neurotransmission after 1-day withdrawal, we used fast-scan cyclic voltammetry (FSCV) to determine whether repeated cocaine alters rapid dopamine release and uptake in the nucleus accumbens (NAc) core and shell. FSCV was performed in urethane anesthetized male Sprague-Dawley rats that had previously received one or seven daily injections of saline or cocaine (15 mg/kg, ip). In response to acute cocaine, subjects showed increased dopamine overflow that resulted from both increased dopamine release and slowed dopamine uptake. One-day cocaine pre-exposure, however, did not alter dopaminergic responses to a subsequent cocaine challenge. In contrast, 7-day cocaine-treated subjects showed a potentiated rapid dopamine response in both the core and shell after an acute cocaine challenge. In addition, kinetic analysis during the cocaine challenge showed a greater increase in apparent Km of 7-day cocaine exposed subjects. Together, the data provide the first in vivo demonstration of rapid dopamine sensitization in the NAc core and shell after a short withdrawal period. In addition, the data clearly delineate cocaine's release and uptake effects and suggest that the observed sensitization results from greater uptake inhibition in cocaine pre-exposed subjects.

scholarly journals Long-lasting contribution of dopamine in the nucleus accumbens core, but not dorsal lateral striatum, to sign-tracking

2017 ◽  
Author(s):  
Kurt M. Fraser ◽  
Patricia H. Janak
Keyword(s):  
Nucleus Accumbens ◽  
Nigrostriatal System ◽  
Dopamine Antagonist ◽  
Incentive Salience ◽  
Sprague Dawley ◽  
Nucleus Accumbens Core ◽  
Reversible Inactivation ◽  
Sign Tracking ◽  
Extended Training ◽  
Accumbens Core

AbstractThe attribution of incentive salience to reward-paired cues is dependent on dopamine release in the nucleus accumbens core. These dopamine signals conform to traditional reward-prediction error signals and have been shown to diminish with time. Here we examined if the diminishing dopamine signal in the nucleus accumbens core has functional implications for the expression of sign-tracking, a Pavlovian conditioned response indicative of the attribution of incentive salience to reward-paired cues. Food-restricted male Sprague-Dawley rats were trained in a Pavlovian paradigm in which an insertable lever predicted delivery of food reward in a nearby food cup. After 7 or 14 training sessions, rats received infusions of saline, the dopamine antagonist flupenthixol (100 mM), or the GABA agonists baclofen and muscimol (0.5 mM baclofen/0.05 mM muscimol) into the nucleus accumbens core or the dorsal lateral striatum. Dopamine antagonism within the nucleus accumbens core attenuated sign-tracking, whereas reversible inactivation did not affect sign-tracking but increased non-specific food cup checking behaviors. Neither drug in the dorsal lateral striatum affected sign-tracking behavior. Critically, extended training did not alter these effects. Though extended experience with an incentive stimulus may reduce cue-evoked dopamine in the nucleus accumbens core, this does not alter the function of dopamine in this region to promote Pavlovian cue approach nor result in the recruitment of dorsal lateral striatal systems for this behavior. These data support the notion that dopamine within the mesoaccumbal system, but not the nigrostriatal system, contributes critically to incentive motivational processes independent of the length of training.AbbreviationsDLSdorsal lateral striatumGTgoal-trackerINintermediate responderNAcCnucleus accumbens coreSTsign-tracker

scholarly journals Electroacupuncture Suppresses Discrete Cue-Evoked Heroin-Seeking and Fos Protein Expression in the Nucleus Accumbens Core in Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Sheng Liu ◽  
Fenglei Zhu ◽  
Miaojun Lai ◽  
Limin Sun ◽  
Yijun Liu ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Therapeutic Benefit ◽  
Sprague Dawley ◽  
Contextual Cues ◽  
Self Administration ◽  
Nucleus Accumbens Core ◽  
Beneficial Effects ◽  
Fos Protein ◽  
Sprague Dawley Rats ◽  
Seeking Behavior

Relapse to drug seeking was studied using a rodent model of reinstatement induced by exposure to drug-related cues. Here, we used intravenous drug self-administration procedures in rats to further investigate the beneficial effects of electroacupuncture (EA) on heroin-seeking behavior in a reinstatement model of relapse. We trained Sprague-Dawley rats to nose-poke for i.v. heroin either daily for 4 h or 25 infusions for 14 consecutive days. Then the rats were abstinent from heroin for two weeks. 2 Hz EA stimulation was conducted once daily for 14 days during heroin abstinence. We tested these animals for contextual and discrete cue-induced reinstatement of active responses. We also applied immunohistochemistry to detect Fos-positive nuclei in the nucleus accumbens (NACc) core and shell after reinstatement test. We found that active responses elicited by both contextual cues and discrete cues were high in the rats trained with heroin than in saline controls. EA treatment significantly reduced active responses elicited by discrete cues. EA stimulation attenuated Fos expression in the core but not the shell of the NACc. Altogether, these results highlight the therapeutic benefit of EA in preventing relapse to drug addiction.

scholarly journals Heroin Cues Reveal Astroglial Heterogeneity in the Nucleus Accumbens Core

2020 ◽  
Author(s):  
Anna Kruyer ◽  
Peter W. Kalivas
Keyword(s):  
Nucleus Accumbens ◽  
Glutamate Uptake ◽  
Glutamate Release ◽  
Surface Expression ◽  
Actin Binding ◽  
Synapsin I ◽  
Self Administration ◽  
Nucleus Accumbens Core ◽  
Distinct Subpopulation ◽  
Accumbens Core

ABSTRACTBACKGROUNDCues predicting heroin delivery induce heroin seeking by initiating synaptic glutamate release in the nucleus accumbens core. The intensity of heroin seeking is negatively modulated by cue-induced increases in synaptic proximity of astrocytes. Glutamate-driven heroin seeking is also negatively regulated by compounds that promote glutamate uptake through the astrocytic transporter GLT-1. We hypothesized that the cue-induced increase in astrocyte synaptic proximity reduces heroin seeking by increasing GLT-1 synaptic proximity.METHODSRats were trained to self-administer heroin or sucrose before undergoing extinction and cued reinstatement of heroin or sucrose seeking. We used confocal microscopy to assess expression and co-registration of GLT-1 with the synaptic marker Synapsin I in the nucleus accumbens core.RESULTSExtinction from heroin, but not sucrose self-administration, downregulated GLT-1. Heroin cues increased surface expression of GLT-1 in parallel with heroin seeking, but counter to expectations, the increase was not proximal to synapses identified by Synapsin I. In fact, astroglia showing cue-induced increased surface expression of GLT-1 constituted a distinct subpopulation of astroglia from those showing increased synaptic proximity. Supporting discrete mechanisms, preventing cue-evoked increases in astrocyte synaptic proximity by knocking down the astroglial-selective actin binding protein ezrin did not impact cue-induced increases in GLT-1 surface expression.CONCLUSIONSOur data demonstrate that heroin-paired cues elicit two transient adaptations in astrocytes in the nucleus accumbens core, restoration of synaptic proximity and increased surface expression of GLT-1. Each adaptation occurs in largely non-overlapping subpopulations of astrocytes, but both adaptations appear to dampen reinstated heroin seeking.

scholarly journals Amperometric measurements of cocaine cue and novel context-evoked glutamate and nitric oxide release in the nucleus accumbens core

2019 ◽  
Author(s):  
BM Siemsen ◽  
JA McFaddin ◽  
K Haigh ◽  
AG Brock ◽  
MN Leath ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nucleus Accumbens ◽  
Temporal Dynamics ◽  
Glutamate Release ◽  
Self Administration ◽  
Nucleus Accumbens Core ◽  
Nitric Oxide Release ◽  
Cocaine Seeking ◽  
No Release ◽  
Accumbens Core

AbstractCue-induced reinstatement of cocaine seeking after self-administration (SA) and extinction relies on glutamate release in the nucleus accumbens core (NAcore), which in turn activates neuronal nitric oxide synthase (nNOS) interneurons. Nitric oxide (NO) is required for structural plasticity in NAcore medium spiny neurons (MSNs), as well as cued cocaine seeking. However, NO release in the NAcore during reinstatement has yet to be directly measured. Further, the temporal relationship between glutamate release, and the induction of a NO response also remains unknown. Using wireless amperometric recordings in awake behaving rat, we quantified the magnitude and temporal dynamics of novel context- and cue-induced reinstatement-evoked glutamate and NO release in the NAcore. We found that re-exposure to cocaine-conditioned stimuli following SA and extinction increased extracellular glutamate, leading to release of NO in the NAcore. In contrast, exposing drug-naïve rats to a novel context led to a lower magnitude rise in glutamate in the NAcore relative to cue-induced reinstatement. Interestingly, novel context exposure evoked a higher magnitude NO response relative to cue-induced reinstatement. Despite differences in magnitude, novel context evoked-NO release in the NAcore was also temporally delayed when compared to glutamate. These results demonstrate a dissociation between the magnitude of cocaine cue- and novel context-evoked glutamate and NO release in the NAcore, yet similarity in the temporal dynamics of their release. Together, these data contribute to a greater understanding of the relationship between glutamate and NO, two neurotransmitters implicated in encoding the valence of distinct contextual stimuli.

scholarly journals The Basolateral amygdala → Nucleus Accumbens core circuit mediates the conditioned reinforcing effects of cocaine-paired cues on cocaine seeking

2020 ◽  
Author(s):  
Mickaël Puaud ◽  
Alejandro Higuera-Matas ◽  
Paul Brunault ◽  
Barry J. Everitt ◽  
David Belin
Keyword(s):  
Nucleus Accumbens ◽  
Basolateral Amygdala ◽  
Major Influence ◽  
Sprague Dawley ◽  
Nucleus Accumbens Core ◽  
Cocaine Seeking ◽  
Control Virus ◽  
Reinforcing Effects ◽  
The Impact ◽  
Accumbens Core

AbstractIndividuals addicted to cocaine spend much of their time foraging for the drug. Pavlovian drug-associated conditioned stimuli exert a major influence on the initiation and maintenance of drug seeking often long into abstinence, especially when presented response-contingently, acting as conditioned reinforcers that bridge delays to drug use. The acquisition of cue-controlled cocaine seeking has been shown to depend on functional interactions between the basolateral amygdala (BLA) and the core of the nucleus accumbens (NAcC). However, the precise neuronal circuits underlying the acquisition of cue-controlled cocaine seeking behaviour have not been elucidated. Here we used a projection-specific Cre-dependent DREADD-mediated causal approach to test the hypothesis that the direct projections from the BLA to the NAcC are required for the acquisition of cue-controlled cocaine seeking behaviour. In Sprague Dawley rats with cre-mediated expression of the inhibitory DREADD Hm4Di in the NAcC projecting BLA neurons, treatment with CNO, but not vehicle, selectively prevented the impact of cocaine-associated conditioned reinforcement on cocaine seeking under a second-order schedule of reinforcement. This effect was attributable to the chemogenetic inhibition of the NAcC projecting BLA neurons as it was reversible, and absent in CNO-treated rats expressing an empty control virus. In contrast, chemogenetic inhibition of the anterior insula, which receives collateral projections from NAcC projecting BLA neurons, was without effect. These data demonstrate that the acquisition of cue-controlled cocaine seeking that depends on the conditioned reinforcing effects of cocaine cues require activity in the direct projections from the basolateral amygdala to the nucleus accumbens core.

scholarly journals CB1R activation in nucleus accumbens core promotes stress-induced reinstatement of cocaine seeking by elevating extracellular glutamate in a drug-paired context

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrea S. Guzman ◽  
Maria P. Avalos ◽  
Laura N. De Giovanni ◽  
Pia V. Euliarte ◽  
Marianela A. Sanchez ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Restraint Stress ◽  
Glutamate Release ◽  
Local Administration ◽  
Glutamatergic Transmission ◽  
Nucleus Accumbens Core ◽  
Extracellular Glutamate ◽  
Cannabinoid Type 1 Receptor ◽  
Cocaine Seeking

AbstractPreclinical models of stress-induced relapse to drug use have shown that the dysregulation of glutamatergic transmission within the nucleus accumbens (NA) contributes notably to the reinstatement of cocaine-seeking behavior in rodents. In this sense, there has been increasing interest in the cannabinoid type-1 receptor (CB1R), due to its crucial role in modulating glutamatergic neurotransmission within brain areas involved in drug-related behaviors. This study explored the involvement of CB1R within the NA subregions in the restraint stress-induced reinstatement of cocaine-conditioned place preference (CPP), as well as in the regulation of glutamatergic transmission, by using a pharmacological approach and the in vivo microdialysis sampling technique in freely moving rats. CB1R blockade by the antagonist/inverse agonist AM251 (5 nmol/0.5 μl/side) or CB1R activation by the agonist ACEA (0.01 fmol/0.5 μl/side), prevented or potentiated restraint stress-induced reinstatement of cocaine-CPP, respectively, after local administration into NAcore, but not NAshell. In addition, microdialysis experiments demonstrated that restraint stress elicited a significant increase in extracellular glutamate in NAcore under reinstatement conditions, with the local administration of AM251 or ACEA inhibiting or potentiating this, respectively. Interestingly, this rise specifically corresponded to the cocaine-associated CPP compartment. We also showed that this context-dependent change in glutamate paralleled the expression of cocaine-CPP, and disappeared after the extinction of this response. Taken together, these findings demonstrated the key role played by CB1R in mediating reinstatement of cocaine-CPP after restraint stress, through modulation of the context-specific glutamate release within NAcore. Additionally, CB1R regulation of basal extracellular glutamate was demonstrated and proposed as the underlying mechanism.

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