The effects of nucleus accumbens core and shell lesions on intravenous heroin self-administration and the acquisition of drug-seeking behaviour under a second-order schedule of heroin reinforcement

2000 ◽  
Vol 153 (4) ◽  
pp. 464-472 ◽  
Author(s):  
D.M. Hutcheson ◽  
John A. Parkinson ◽  
Trevor W. Robbins ◽  
Barry J. Everitt
Keyword(s):  
Nucleus Accumbens ◽  
Second Order ◽  
Self Administration ◽  
Nucleus Accumbens Core ◽  
Drug Seeking ◽  
Accumbens Core

scholarly journals ∆9-Tetrahydrocannabinol Self-Administration Induces Cell-Type Specific Adaptations and cFOS Expression in the Nucleus Accumbens Core

2021 ◽  
Author(s):  
Daniela Neuhofer ◽  
Constanza Garcia-Keller ◽  
Madeline Hohmeister ◽  
Kailyn Seidling ◽  
Lauren Beloate ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Synaptic Transmission ◽  
Drugs Of Abuse ◽  
Self Administration ◽  
Nucleus Accumbens Core ◽  
Drug Seeking ◽  
Glutamate Transmission ◽  
Cell Type Specific ◽  
Activity Marker ◽  
Accumbens Core

Abstract Given that 30% of chronic cannabis users develop cannabis use disorder (CUD), it is critical to identify neuroadaptations that contribute to this disease. The nucleus accumbens core (NAcore) is important for drug seeking and ~ 90% of all NAcore neurons are divided into D1- and D2-medium spiny neurons (MSNs) that serve opposing roles in drug seeking. Drugs of abuse induce D1- and D2-MSN specific adaptations but whether ∆9-tetrahydrocannabinol (THC) use initiates similar neuroadaptations is unknown. D1- and D2-Cre transgenic rats were transfected with Cre-dependent reporters and trained to self-administer THC + cannabidiol (THC + CBD). After extinction training dendritic spine morphology, glutamate transmission, CB1R function and cFOS expression were quantified. We found that extinction from THC + CBD induced a loss of large spine heads in D1- but not D2-MSNs and a commensurate reduction in glutamate synaptic transmission. Also, CB1R function was impaired on glutamatergic synapses onto D1-MSNs and this was paralleled by an augmented capacity to potentiate glutamate transmission in D1-MSNs. CB1R function and glutamate synaptic transmission on D2-MSN synapses were unaffected by THC + CBD use. Using cFOS expression as an activity marker, we found that D1-MSNs activity remained unchanged after extinction from THC + CBD but significantly increased after 60 minutes cue-induced drug seeking. Surprisingly, the percentage of D2-MSNs expressing cFOS decreased after extinction from THC + CBD and this decrease was restored by drug cues. Thus, glutamatergic adaptations in D1-MSNs partially predict activity changes and pose modulating CB1R function that is down-regulated selectively at D1-MSN synapses as a potential treatment strategy for CUD.

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.

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
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