scholarly journals Nucleus accumbens cholinergic interneurons oppose cue-motivated behavior

2019 ◽  
Author(s):  
Anne L. Collins ◽  
Tara J. Aitken ◽  
I-Wen Huang ◽  
Christine Shieh ◽  
Venuz Y. Greenfield ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Female Rats ◽  
Nucleus Accumbens Core ◽  
Cholinergic Interneurons ◽  
Reward Seeking ◽  
Motivated Behavior ◽  
Male And Female Rats ◽  
Seeking Behavior

ABSTRACTBackgroundEnvironmental reward-predictive stimuli provide a major source of motivation for adaptive reward pursuit behavior. This cue-motivated behavior is known to be mediated by the nucleus accumbens core (NAc). The cholinergic interneurons in the NAc are tonically active and densely arborized and, thus, well-suited to modulate NAc function. But their causal contribution to adaptive behavior remains unknown. Here we investigated the function of NAc cholinergic interneurons in cue-motivated behavior.MethodsTo do this, we used chemogenetics, optogenetics, pharmacology, and a translationally analogous Pavlovian-to-instrumental transfer behavioral task designed to assess the motivating influence of a reward-predictive cue over reward-seeking actions in male and female rats.ResultsThe data show that NAc cholinergic interneuron activity is necessary and sufficient to oppose the motivating influence of appetitive cues. Chemogenetic inhibition of NAc cholinergic interneurons augmented cue-motivated behavior. Optical stimulation of acetylcholine release from NAc cholinergic interneurons prevented cues from invigorating reward-seeking behavior, an effect that was mediated by activation of β2-containing nicotinic acetylcholine receptors.ConclusionsThus, NAc cholinergic interneurons provide a critical regulatory influence over adaptive cue-motivated behavior and, therefore, are a potential therapeutic target for the maladaptive cue-motivated behavior that marks many psychiatric conditions, including addiction and depression.

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 Ceftriaxone and mGlu2/3 interactions in the nucleus accumbens core affect the reinstatement of cocaine-seeking in male and female rats

2020 ◽  
Vol 237 (7) ◽  
pp. 2007-2018 ◽  
Author(s):  
Carly N. Logan ◽  
Allison R. Bechard ◽  
Peter U. Hamor ◽  
Lizhen Wu ◽  
Marek Schwendt ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Female Rats ◽  
Nucleus Accumbens Core ◽  
Male And Female ◽  
Male And Female Rats ◽  
Cocaine Seeking ◽  
Core Affect ◽  
Accumbens Core

scholarly journals Ceftriaxone and mGlu2/3 interactions in the nucleus accumbens core affect the reinstatement of cocaine-seeking in male and female rats

2020 ◽  
Author(s):  
Carly N. Logan ◽  
Allison R. Bechard ◽  
Peter U. Hamor ◽  
Lizhen Wu ◽  
Marek Schwendt ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Surface Expression ◽  
Receptor Expression ◽  
Female Rats ◽  
Beta Lactam ◽  
Nucleus Accumbens Core ◽  
Male And Female ◽  
Male And Female Rats ◽  
Cocaine Seeking ◽  
Accumbens Core

AbstractRationaleThe beta-lactam antibiotic ceftriaxone reliably attenuates the reinstatement of cocaine-seeking. While the restoration of nucleus accumbens core (NA core) GLT-1 expression is necessary for ceftriaxone to attenuate reinstatement, AAV-mediated GLT-1 overexpression is not sufficient to attenuate reinstatement and does not prevent glutamate efflux during reinstatement.AimsHere, we test the hypothesis that ceftriaxone attenuates reinstatement through interactions with glutamate autoreceptors mGlu2 and mGlu3 in the NA core.MethodsMale and female rats self-administered cocaine for 12 days followed by 2-3 weeks of extinction training. During the last 6-10 days of extinction, rats received ceftriaxone (200 mg/kg IP) or vehicle. In experiment 1, rats were killed, and NA core tissue was biotinylated for assessment of total and surface expression of mGlu2 and mGlu3 via western blotting. In experiment 2, we tested the hypothesis that mGlu2/3 signaling is necessary for ceftriaxone to attenuate cue- and cocaine-primed reinstatement by administering bilateral intra-NA core infusion of mGlu2/3 antagonist LY341495 or vehicle immediately prior to reinstatement testing.ResultsmGlu2 expression was reduced by cocaine and restored by ceftriaxone. There were no effects of cocaine or ceftriaxone on mGlu3 expression. We observed no effects of estrus on expression of either protein. The antagonism of mGlu2/3 in the NA core during both cue- and cocaine-primed reinstatement tests prevented ceftriaxone from attenuating reinstatement.ConclusionsThese results indicate that ceftriaxone’s effects depend on mGlu2/3 function and possibly mGlu2 receptor expression. Future work will test this hypothesis by manipulating mGlu2 expression in pathways that project to the NA core.

scholarly journals A unique multi-synaptic mechanism regulates dopamine release in the nucleus accumbens during adolescence

2020 ◽  
Author(s):  
Elizabeth G. Pitts ◽  
Taylor A. Stowe ◽  
Mark J. Ferris
Keyword(s):  
Nucleus Accumbens ◽  
Nicotinic Acetylcholine Receptors ◽  
Acetylcholine Receptors ◽  
Dopamine Release ◽  
Gaba Release ◽  
Behavioral Changes ◽  
Male Rats ◽  
Nucleus Accumbens Core ◽  
Fast Scan Cyclic Voltammetry ◽  
Transition Into Adulthood

SummaryAdolescence is characterized by changes in reward-related behaviors, social behaviors, and decision making. These behavioral changes are necessary for the transition into adulthood, but they also increase vulnerability to the development of a range of psychiatric disorders. Major reorganization of the dopamine system during adolescence is thought to underlie, in part, the behavioral changes and increased vulnerability. Here, we utilized fast scan cyclic voltammetry to examine differences in regulation of dopamine release in the nucleus accumbens core of adolescent and adult male rats. We found that differences between adolescent and adult stimulated dopamine release is driven by a unique multisynaptic mechanism in early adolescence involving acetylcholine acting at α6-containing nicotinic acetylcholine receptors to mediate inhibition of dopamine via GABA release. These changes in dopamine regulation across adolescence provides a springboard for our understanding of basic brain development and targeted therapy for a range of psychiatric conditions that emerge in adolescence.

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