The effects of excitotoxic lesions of the nucleus accumbens core or shell regions on intravenous heroin self-administration in rats

2000 ◽  
Vol 153 (4) ◽  
pp. 455-463 ◽  
Author(s):  
Helen L. Alderson ◽  
John A. Parkinson ◽  
Trevor W. Robbins ◽  
Barry J. Everitt
Keyword(s):  
Nucleus Accumbens ◽  
Self Administration ◽  
Nucleus Accumbens Core ◽  
Accumbens Core

scholarly journals Increased presynaptic regulation of dopamine neurotransmission in the nucleus accumbens core following chronic ethanol self-administration in female macaques

2016 ◽  
Vol 233 (8) ◽  
pp. 1435-1443 ◽  
Author(s):  
Cody A. Siciliano ◽  
Erin S. Calipari ◽  
Jordan T. Yorgason ◽  
David M. Lovinger ◽  
Yolanda Mateo ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Chronic Ethanol ◽  
Self Administration ◽  
Nucleus Accumbens Core ◽  
Presynaptic Regulation ◽  
Accumbens Core

scholarly journals Metformin in nucleus accumbens core reduces cue-induced cocaine seeking in male and female rats

2021 ◽  
Author(s):  
Amy Chan ◽  
Alexis Willard ◽  
Sarah Mulloy ◽  
Noor Ibrahim ◽  
Allegra Sciaccotta ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Female Rats ◽  
Therapeutic Effects ◽  
Self Administration ◽  
Nucleus Accumbens Core ◽  
Male And Female ◽  
Male And Female Rats ◽  
Cocaine Seeking ◽  
Ampk Activity ◽  
Accumbens Core

This study investigated the potential therapeutic effects of the FDA-approved drug metformin on cue-induced reinstatement of cocaine seeking. Metformin (dimethyl-biguanide) is a first-line treatment for type II diabetes that, among other mechanisms, is involved in the activation of adenosine monophosphate activated protein kinase (AMPK). Cocaine self-administration and extinction is associated with decreased levels of phosphorylated AMPK within the nucleus accumbens core (NAcore). Previously it was shown that increasing AMPK activity in the NAcore decreased cue-induced reinstatement of cocaine seeking. Decreasing AMPK activity produced the opposite effect. The goal of the present study was to determine if metformin in the NAcore reduces cue-induced cocaine seeking in adult male and female Sprague Dawley rats. Rats were trained to self-administer cocaine followed by extinction prior to cue-induced reinstatement trials. Metformin microinjected in the NAcore attenuated cue-induced reinstatement in male and female rats. Importantly, metformin's effects on cocaine seeking were not due to a general depression of spontaneous locomotor activity. In female rats, metformin's effects did generalize to a reduction in cue-induced reinstatement of sucrose seeking. These data support a potential role for metformin as a pharmacotherapy for cocaine use disorder, but warrant caution given the potential for metformin's effects to generalize to a natural reward in female rats.

scholarly journals Effects of Methamphetamine Self-Administration and Extinction on Astrocyte Structure and Function in the Nucleus Accumbens Core

Neuroscience ◽  
2019 ◽  
Vol 406 ◽  
pp. 528-541 ◽  
Author(s):  
B.M. Siemsen ◽  
C.M. Reichel ◽  
K.C. Leong ◽  
C. Garcia-Keller ◽  
C.D. Gipson ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Structure And Function ◽  
Self Administration ◽  
Nucleus Accumbens Core ◽  
And Function ◽  
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 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.

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