scholarly journals Long‐access to cocaine self‐administration dysregulates the glutamate synapse in the nucleus accumbens core of serotonin transporter knockout rats

Author(s):  
Lucia Caffino ◽  
Francesca Mottarlini ◽  
Giorgia Targa ◽  
Michel M. M. Verheij ◽  
Judith Homberg ◽  
...  
2016 ◽  
Vol 233 (8) ◽  
pp. 1435-1443 ◽  
Author(s):  
Cody A. Siciliano ◽  
Erin S. Calipari ◽  
Jordan T. Yorgason ◽  
David M. Lovinger ◽  
Yolanda Mateo ◽  
...  

2021 ◽  
Author(s):  
Amy Chan ◽  
Alexis Willard ◽  
Sarah Mulloy ◽  
Noor Ibrahim ◽  
Allegra Sciaccotta ◽  
...  

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.


Neuroscience ◽  
2019 ◽  
Vol 406 ◽  
pp. 528-541 ◽  
Author(s):  
B.M. Siemsen ◽  
C.M. Reichel ◽  
K.C. Leong ◽  
C. Garcia-Keller ◽  
C.D. Gipson ◽  
...  

2021 ◽  
Author(s):  
Benjamin M. Siemsen ◽  
Sarah M. Barry ◽  
Kelsey Vollmer ◽  
Lisa M. Green ◽  
Ashley G. Brock ◽  
...  

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.


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

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