Nucleus accumbens

The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the nucleus accumbens septi, Latin for 'nucleus adjacent to the septum') is a region in the basal forebrain rostral to the preoptic area of the hypothalamus.<ref name="Carlson, Neil R 2013">Template:Cite book Template:Page needed</ref> The nucleus accumbens and the olfactory tubercle collectively form the ventral striatum. The ventral striatum and dorsal striatum collectively form the striatum, which is the main component of the basal ganglia.<ref>Nucleus Accumbens</ref> The dopaminergic neurons of the mesolimbic pathway project onto the GABAergic medium spiny neurons of the nucleus accumbens and olfactory tubercle.<ref name="Dopaminergic pathways and reward system review">Template:Cite journal
Figure 3: The ventral striatum and self-administration of amphetamine</ref><ref name="NAcc function" /> Each cerebral hemisphere has its own nucleus accumbens, which can be divided into two structures: the nucleus accumbens core and the nucleus accumbens shell. These substructures have different morphology and functions.

Different NAcc subregions (core vs shell) and neuron subpopulations within each region (D1-type vs D2-type medium spiny neurons) are responsible for different cognitive functions.<ref name="NAcc core and shell">Template:Cite journal</ref><ref name="Reward and aversion MSNs" /> As a whole, the nucleus accumbens has a significant role in the cognitive processing of motivation, aversion, reward (i.e., incentive salience, pleasure, and positive reinforcement), and reinforcement learning (e.g., Pavlovian-instrumental transfer);<ref name="NAcc function" /><ref name="Aversion neurons">Template:Cite journal</ref><ref name="Malenka NAcc" /><ref name="Mesolimbic dopamine in motivation and PIT" /><ref name="Learning+Motivation in PIT - neural mechanisms review" /> hence, it has a significant role in addiction.<ref name="NAcc function">Template:Cite book</ref><ref name="Malenka NAcc">Template:Cite book</ref> In addition, part of the nucleus accumbens core is centrally involved in the induction of slow-wave sleep.<ref name="Zinc & sleep 2017 review" /><ref name="Nucleus accumbens - Slow-wave sleep" /><ref name="Slow-wave sleep and NAcc core A2AR neurons - Sept 2017 primary source" /><ref name="Striatal A2AR neurons and sleep - Oct 2017 primary source" /> The nucleus accumbens plays a lesser role in processing fear (a form of aversion), impulsivity, and the placebo effect.<ref>Template:Cite journal</ref><ref name="placebo effect">Template:Cite journal</ref><ref name="pmid20831892">Template:Cite journal</ref> It is involved in the encoding of new motor programs as well.<ref name="NAcc function" />

Structure

The nucleus accumbens is an aggregate of neurons which is described as having an outer shell and an inner core.<ref name="NAcc function" />

Input

Major glutamatergic inputs to the nucleus accumbens include the prefrontal cortex (particularly the prelimbic cortex and infralimbic cortex), basolateral amygdala, ventral hippocampus, thalamic nuclei (specifically the midline thalamic nuclei and intralaminar nuclei of the thalamus), and glutamatergic projections from the ventral tegmental area (VTA).<ref name="Rapid+transient drug-induced synaptic plasticity">Template:Cite journal
Figure 1: Glutamatergic afferents to the nucleus accumbens involved in addictive behavior</ref> The nucleus accumbens receives dopaminergic inputs from the ventral tegmental area, which connect via the mesolimbic pathway. The nucleus accumbens is often described as one part of a cortico-basal ganglia-thalamo-cortical loop.<ref name="Striatal efferents, afferents, and colocalized receptors in dMSNs and iMSNs" />

Dopaminergic inputs from the VTA modulate the activity of GABAergic neurons within the nucleus accumbens. These neurons are activated directly or indirectly by euphoriant drugs (e.g., amphetamine, opiates, etc.) and by participating in rewarding experiences (e.g., sex, music, exercise, etc.).<ref name="Nestler">Template:Cite journal</ref><ref name="ΔFosB reward" />

Another major source of input comes from the CA1 and ventral subiculum of the hippocampus to the dorsomedial area of the nucleus accumbens. Slight depolarizations of cells in the nucleus accumbens correlates with positivity of the neurons of the hippocampus, making them more excitable. The correlated cells of these excited states of the medium spiny neurons in the nucleus accumbens are shared equally between the subiculum and CA1. The subiculum neurons are found to hyperpolarize (increase negativity) while the CA1 neurons "ripple" (fire > 50 Hz) in order to accomplish this priming.<ref>Template:Cite journal</ref>

The nucleus accumbens is one of the few regions that receives a high density of histaminergic projections from the tuberomammillary nucleus (the sole source of histamine neurons in the brain).<ref name="Histamine pathways">Template:Cite book</ref>

Output

The output neurons of the nucleus accumbens send axonal projections to the basal ganglia and the ventral analog of the globus pallidus, known as the ventral pallidum (VP). The VP, in turn, projects to the medial dorsal nucleus of the dorsal thalamus, which projects to the prefrontal cortex as well as back to the ventral and to dorsal striatum. Other efferents from the nucleus accumbens include connections with the tail of the ventral tegmental area,<ref name="Brake">Template:Cite journal</ref> substantia nigra, and the reticular formation of the pons.<ref name="Carlson, Neil R 2013"/>

Shell

The nucleus accumbens shell (NAcc shell) is a substructure of the nucleus accumbens. The shell and core together form the entire nucleus accumbens.

Location: The shell is the outer region of the nucleus accumbens, and – unlike the core – is considered to be part of the extended amygdala, located at its rostral pole.

Cell types: Neurons in the nucleus accumbens are mostly medium spiny neurons (MSNs) containing mainly D1-type (i.e., DRD1 and DRD5) or D2-type (i.e., DRD2, DRD3, and DRD4) dopamine receptors. A subpopulation of MSNs contain both D1-type and D2-type receptors, with approximately 40% of striatal MSNs expressing both DRD1 and DRD2 mRNA.<ref name="Striatal efferents, afferents, and colocalized receptors in dMSNs and iMSNs" /><ref name="Ventral striatum">Template:Cite journal</ref><ref name="MSN 40% mixed-type with DRD1 and DRD2">Template:Cite journal</ref> These mixed-type NAcc MSNs with both D1-type and D2-type receptors are mostly confined to the NAcc shell.<ref name="Striatal efferents, afferents, and colocalized receptors in dMSNs and iMSNs">Template:Cite journal</ref> The neurons in the shell, as compared to the core, have a lower density of dendritic spines, less terminal segments, and less branch segments than those in the core. The shell neurons project to the subcommissural part of the ventral pallidum as well as the ventral tegmental area and to extensive areas in the hypothalamus and extended amygdala.<ref name=pmid18654637/><ref>Template:Cite journal</ref><ref name=pmid7906426>Template:Cite book</ref>

Function: The shell of the nucleus accumbens is involved in the cognitive processing of reward, including subjective "liking" reactions to certain pleasurable stimuli, motivational salience, and positive reinforcement.<ref name="NAcc function" /><ref name="NAcc core and shell" /><ref name="Pleasure system" /><ref name="pmid24107968">Template:Cite journal</ref> That NAcc shell has also been shown to mediate specific Pavlovian-instrumental transfer, a phenomenon in which a classically conditioned stimulus modifies operant behavior.<ref name="Pavlovian-instrumental transfer review" /><ref name="Mesolimbic dopamine in motivation and PIT" /><ref name="Learning+Motivation in PIT - neural mechanisms review" /> A "hedonic hotspot" or pleasure center which is responsible for the pleasurable or "liking" component of some intrinsic rewards is also located in a small compartment within the medial NAcc shell.<ref name="Pleasure system">Template:Cite journal</ref><ref name="Mapping brain circuits">Template:Cite journal

• Figure 3: Neural circuits underlying motivated 'wanting' and hedonic 'liking'.</ref><ref name=Berridge2>Template:Cite journal</ref> Addictive drugs have a larger effect on dopamine release in the shell than in the core.<ref name="NAcc function" />

Core

The nucleus accumbens core (NAcc core) is the inner substructure of the nucleus accumbens.

Location: The nucleus accumbens core is part of the ventral striatum, located within the basal ganglia. Cell types: The core of the NAcc is made up mainly of medium spiny neurons containing mainly D1-type or D2-type dopamine receptors. The D1-type medium spiny neurons mediate reward-related cognitive processes,<ref name="NAcc core and shell" /><ref name="NAcc regional neuron subtypes">Template:Cite journal</ref><ref name="Reward and the NAcc shell vs core">Template:Cite journal</ref> whereas the D2-type medium spiny neurons mediate aversion-related cognition.<ref name="Reward and aversion MSNs" /> The neurons in the core, as compared to the neurons in the shell, have an increased density of dendritic spines, branch segments, and terminal segments. From the core, the neurons project to other sub-cortical areas such as the globus pallidus and the substantia nigra. GABA is one of the main neurotransmitters in the NAcc, and GABA receptors are also abundant.<ref name=pmid18654637>Template:Cite journal</ref><ref name=pmid7906426/>

Function: The nucleus accumbens core is involved in the cognitive processing of motor function related to reward and reinforcement and the regulation of slow-wave sleep.<ref name="NAcc function" /><ref name="Zinc & sleep 2017 review" /><ref name="Nucleus accumbens - Slow-wave sleep" /><ref name="Slow-wave sleep and NAcc core A2AR neurons - Sept 2017 primary source" /> Specifically, the core encodes new motor programs which facilitate the acquisition of a given reward in the future.<ref name="NAcc function" /> The indirect pathway (i.e., D2-type) neurons in the NAcc core which co-express adenosine A_2A receptors activation-dependently promote slow-wave sleep.<ref name="Zinc & sleep 2017 review" /><ref name="Nucleus accumbens - Slow-wave sleep" /><ref name="Slow-wave sleep and NAcc core A2AR neurons - Sept 2017 primary source" /> The NAcc core has also been shown to mediate general Pavlovian-instrumental transfer, a phenomenon in which a classically conditioned stimulus modifies operant behavior.<ref name="Pavlovian-instrumental transfer review">Template:Cite journal</ref><ref name="Mesolimbic dopamine in motivation and PIT">Template:Cite book</ref><ref name="Learning+Motivation in PIT - neural mechanisms review">Template:Cite book</ref>

Cell types

Approximately 95% of neurons in the NAcc are GABAergic medium spiny neurons (MSNs) which primarily express either D1-type or D2-type receptors;<ref name="Nestler" /> about 1–2% of the remaining neuronal types are large aspiny cholinergic interneurons and another 1–2% are GABAergic interneurons.<ref name="Nestler" /> Compared to the GABAergic MSNs in the shell, those in the core have an increased density of dendritic spines, branch segments, and terminal segments. From the core, the neurons project to other sub-cortical areas such as the globus pallidus and the substantia nigra. GABA is one of the main neurotransmitters in the NAcc, and GABA receptors are also abundant.<ref name=pmid18654637/><ref name=pmid7906426/> These neurons are also the main projection or output neurons of the nucleus accumbens.

Neurochemistry

Some of the neurotransmitters, neuromodulators, and hormones that signal through receptors within the nucleus accumbens include:

Dopamine: Dopamine is released into the nucleus accumbens following exposure to rewarding stimuli, including recreational drugs like substituted amphetamines, cocaine, nicotine and morphine.<ref>Template:Cite journal</ref><ref name="Shell vs core in addiction" />

Phenethylamine and tyramine: Phenethylamine and tyramine are trace amines which are synthesized in neurons that express the aromatic amino acid hydroxylase (AADC) enzyme, which includes all dopaminergic neurons.<ref name="E Weihe">Template:Cite journal</ref> Both compounds function as dopaminergic neuromodulators which regulate the reuptake and release of dopamine into the Nacc via interactions with VMAT2 and TAAR1 in the axon terminal of mesolimbic dopamine neurons.

Glucocorticoids and dopamine: Glucocorticoid receptors are the only corticosteroid receptors in the nucleus accumbens shell. L-DOPA, steroids, and specifically glucocorticoids are currently known to be the only known endogenous compounds that can induce psychotic problems, so understanding the hormonal control over dopaminergic projections with regard to glucocorticoid receptors could lead to new treatments for psychotic symptoms. A recent study demonstrated that suppression of the glucocorticoid receptors led to a decrease in the release of dopamine, which may lead to future research involving anti-glucocorticoid drugs to potentially relieve psychotic symptoms.<ref>Template:Cite journal</ref>

GABA: A recent study on rats that used GABA agonists and antagonists indicated that GABA_A receptors in the NAcc shell have inhibitory control on turning behavior influenced by dopamine, and GABA_B receptors have inhibitory control over turning behavior mediated by acetylcholine.<ref name=pmid18654637/><ref>Template:Cite journal</ref>

Glutamate: Studies have shown that local blockade of glutamatergic NMDA receptors in the NAcc core impaired spatial learning.<ref name="pmid10495079">Template:Cite journal</ref> Another study demonstrated that both NMDA and AMPA (both glutamate receptors) play important roles in regulating instrumental learning.<ref name="pmid15845096">Template:Cite journal</ref>

Serotonin (5-HT): Overall, 5-HT synapses are more abundant and have a greater number of synaptic contacts in the NAcc shell than in the core. They are also larger and thicker, and contain more large dense core vesicles than their counterparts in the core.

Function

Reward and reinforcement

The nucleus accumbens, being one part of the reward system, plays an important role in processing rewarding stimuli, reinforcing stimuli (e.g., food and water), and those which are both rewarding and reinforcing (addictive drugs, sex, and exercise).<ref name="NAcc function" /><ref name="Natural and drug addictions" /> The predominant response of neurons in the nucleus accumbens to the reward sucrose is inhibition; the opposite is true in response to the administration of aversive quinine.<ref>Template:Cite journal</ref> Substantial evidence from pharmacological manipulation also suggests that reducing the excitability of neurons in the nucleus accumbens is rewarding, as, for example, would be true in the case of μ-opioid receptor stimulation.<ref>Template:Cite journal</ref> The blood oxygen level dependent signal (BOLD) in the nucleus accumbens is selectively increased during the perception of pleasant, emotionally arousing pictures and during mental imagery of pleasant, emotional scenes. However, as BOLD is thought to be an indirect measure of regional net excitation to inhibition, the extent to which BOLD measures valence dependent processing is unknown.<ref name=Costa>Template:Cite journal</ref><ref name=Sabatinelli>Template:Cite journal</ref> Because of the abundance of NAcc inputs from limbic regions and strong NAcc outputs to motor regions, the nucleus accumbens has been described by Gordon Mogensen as the interface between the limbic and motor system.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>

File:Castro2015.jpg

Tuning of appetitive and defensive reactions in the nucleus accumbens shell. (Above) AMPA blockade requires D1 function in order to produce motivated behaviors, regardless of valence, and D2 function to produce defensive behaviors. GABA agonism, on the other hand, does not require dopamine receptor function.(Below)The expansion of the anatomical regions that produce defensive behaviors under stress, and appetitive behaviors in the home environment produced by AMPA antagonism. This flexibility is less evident with GABA agonism.<ref>Template:Cite journal</ref>

The nucleus accumbens is causally related to the experience of pleasure. Microinjections of μ-opioid agonists, δ-opioid agonists or κ-opioid agonists in the rostrodorsal quadrant of the medial shell enhance "liking", while more caudal injections can inhibit disgust reactions, liking reactions, or both.<ref name="Pleasure system"/> The regions of the nucleus accumbens that can be ascribed a causal role in the production of pleasure are limited both anatomically and chemically, as besides opioid agonists only endocannabinoids can enhance liking. In the nucleus accumbens as a whole, dopamine, GABA receptor agonist or AMPA antagonists solely modify motivation, while the same is true for opioid and endocannabinoids outside of the hotspot in the medial shell. A rostro-caudal gradient exists for the enhancement of appetitive versus fearful responses, the latter of which is traditionally thought to require only D1 receptor function, and the former of which requires both D1 and D2 function. One interpretation of this finding, the disinhibition hypothesis, posits that inhibition of accumbens MSNs (which are GABAergic) disinhibits downstream structures, enabling the expression of appetitive or consummatory behaviors.<ref name="Berridge2013">Template:Cite journal</ref> The motivational effects of AMPA antagonists, and to a lesser extent GABA agonists, is anatomically flexible. Stressful conditions can expand the fear inducing regions, while a familiar environment can reduce the size of the fear inducing region. Furthermore, cortical input from the orbitofrontal cortex (OFC) biases the response towards that of appetitive behavior, and infralimbic input, equivalent to the human subgenual cingulate cortex, suppresses the response regardless of valence.<ref name="Pleasure system"/>

The nucleus accumbens is neither necessary nor sufficient for instrumental learning, although manipulations can affect performance on instrumental learning tasks. One task where the effect of NAcc lesions is evident is Pavlovian-instrumental transfer (PIT), where a cue paired with a specific or general reward can enhance instrumental responding. Lesions to the core of the NAcc impair performance after devaluation and inhibit the effect of general PIT. On the other hand, lesions to the shell only impair the effect of specific PIT. This distinction is thought to reflect consummatory and appetitive conditioned responses in the NAcc shell and the NAcc core, respectively.<ref>Template:Cite journal</ref>

In the dorsal striatum, a dichotomy has been observed between D1-MSNs and D2-MSNs, with the former being reinforcing and enhancing locomotion, and the latter being aversive and reducing locomotion. Such a distinction has been traditionally assumed to apply to the nucleus accumbens as well, but evidence from pharmacological and optogenetics studies is conflicting. Furthermore, a subset of NAcc MSNs express both D1 and D2 MSNs, and pharmacological activation of D1 versus D2 receptors need not necessarily activate the neural populations exactly. While most studies show no effect of selective optogenetic stimulation of D1 or D2 MSNs on locomotor activity, one study has reported a decrease in basal locomotion with D2-MSN stimulation. While two studies have reported reduced reinforcing effects of cocaine with D2-MSN activation, one study has reported no effect. NAcc D2-MSN activation has also been reported to enhance motivation, as assessed by PIT, and D2 receptor activity is necessary for the reinforcing effects of VTA stimulation.<ref>Template:Cite journal</ref> A 2018 study reported that D2 MSN activation enhanced motivation via inhibiting the ventral pallidum, thereby disinhibiting the VTA.<ref>Template:Cite journal</ref>

Maternal behavior

An fMRI study conducted in 2005 found that when mother rats were in the presence of their pups the regions of the brain involved in reinforcement, including the nucleus accumbens, were highly active.<ref>Template:Cite journal</ref> Levels of dopamine increase in the nucleus accumbens during maternal behavior, while lesions in this area upset maternal behavior.<ref>Template:Cite journal</ref> When women are presented pictures of unrelated infants, fMRIs show increased brain activity in the nucleus accumbens and adjacent caudate nucleus, proportionate to the degree to which the women find these infants "cute".<ref>Template:Cite journal</ref>

Aversion

Activation of D1-type MSNs in the nucleus accumbens is involved in reward, whereas the activation of D2-type MSNs in the nucleus accumbens promotes aversion.<ref name="Reward and aversion MSNs">Template:Cite journal</ref>

Slow-wave sleep

In late 2017, studies on rodents which utilized optogenetic and chemogenetic methods found that the indirect pathway (i.e., D2-type) medium spiny neurons in the nucleus accumbens core which co-express adenosine A_2A receptors and project to the ventral pallidum are involved in the regulation of slow-wave sleep.<ref name="Zinc & sleep 2017 review">Template:Cite journal</ref><ref name="Nucleus accumbens - Slow-wave sleep" /><ref name="Slow-wave sleep and NAcc core A2AR neurons - Sept 2017 primary source" /><ref name="Striatal A2AR neurons and sleep - Oct 2017 primary source" /> In particular, optogenetic activation of these indirect pathway NAcc core neurons induces slow-wave sleep and chemogenetic activation of the same neurons increases the number and duration of slow-wave sleep episodes.<ref name="Nucleus accumbens - Slow-wave sleep">Template:Cite journal</ref><ref name="Slow-wave sleep and NAcc core A2AR neurons - Sept 2017 primary source">Template:Cite journal</ref><ref name="Striatal A2AR neurons and sleep - Oct 2017 primary source">Template:Cite journal</ref> Chemogenetic inhibition of these NAcc core neurons suppresses sleep.<ref name="Nucleus accumbens - Slow-wave sleep" /><ref name="Slow-wave sleep and NAcc core A2AR neurons - Sept 2017 primary source" /> In contrast, the D2-type medium spiny neurons in the NAcc shell which express adenosine A_2A receptors have no role in regulating slow-wave sleep.<ref name="Nucleus accumbens - Slow-wave sleep" /><ref name="Slow-wave sleep and NAcc core A2AR neurons - Sept 2017 primary source" />

Clinical significance

Addiction

Current models of addiction from chronic drug use involve alterations in gene expression in the mesocorticolimbic projection.<ref name="Nestler" /><ref name="Nestler, Hyman, and Malenka 2">Template:Cite journal</ref><ref name="Addiction genetics">Template:Cite journal</ref> The most important transcription factors that produce these alterations are ΔFosB, cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), and nuclear factor kappa B (NFκB).<ref name="Nestler" /> ΔFosB is the most significant gene transcription factor in addiction since its viral or genetic overexpression in the nucleus accumbens is necessary and sufficient for many of the neural adaptations and behavioral effects (e.g., expression-dependent increases in self-administration and reward sensitization) seen in drug addiction.<ref name="Nestler" /><ref name="NAcc regional neuron subtypes" /><ref name="What the ΔFosB?">Template:Cite journal</ref> ΔFosB overexpression has been implicated in addictions to alcohol (ethanol), cannabinoids, cocaine, methylphenidate, nicotine, opioids, phencyclidine, propofol, and substituted amphetamines, among others.<ref name="Nestler" /><ref name="Nestler, Hyman, and Malenka 2" /><ref name="What the ΔFosB?" /><ref name="Alcoholism ΔFosB">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="MPH ΔFosB">Template:Cite journal</ref> Increases in nucleus accumbens ΔJunD expression can reduce or, with a large increase, even block most of the neural alterations seen in chronic drug abuse (i.e., the alterations mediated by ΔFosB).<ref name="Nestler" />

ΔFosB also plays an important role in regulating behavioral responses to natural rewards, such as palatable food, sex, and exercise.<ref name="Nestler" /><ref name="ΔFosB reward">Template:Cite journal</ref> Natural rewards, like drugs of abuse, induce ΔFosB in the nucleus accumbens, and chronic acquisition of these rewards can result in a similar pathological addictive state through ΔFosB overexpression.<ref name="Nestler" /><ref name="ΔFosB reward" /><ref name="Natural and drug addictions">Template:Cite journal</ref> Consequently, ΔFosB is the key transcription factor involved in addictions to natural rewards as well;<ref name="Nestler" /><ref name="ΔFosB reward"/><ref name="Natural and drug addictions" /> in particular, ΔFosB in the nucleus accumbens is critical for the reinforcing effects of sexual reward.<ref name="ΔFosB reward" /> Research on the interaction between natural and drug rewards suggests that psychostimulants and sexual behavior act on similar biomolecular mechanisms to induce ΔFosB in the nucleus accumbens and possess cross-sensitization effects that are mediated through ΔFosB.<ref name="Natural and drug addictions" /><ref name="Amph and sex addiction">Template:Cite journal</ref>

Similar to drug rewards, non-drug rewards also increase the level of extracellular dopamine in the NAcc shell. Drug-induced dopamine release in the NAcc shell and NAcc core is usually not prone to habituation (i.e., the development of drug tolerance: a decrease in dopamine release from future drug exposure as a result of repeated drug exposure); on the contrary, repeated exposure to drugs that induce dopamine release in the NAcc shell and core typically results in sensitization (i.e., the amount of dopamine that is released in the NAcc from future drug exposure increases as a result of repeated drug exposure). Sensitization of dopamine release in the NAcc shell following repeated drug exposure serves to strengthen stimulus-drug associations (i.e., classical conditioning that occurs when drug use is repeatedly paired with environmental stimuli) and these associations become less prone to extinction (i.e., "unlearning" these classically conditioned associations between drug use and environmental stimuli becomes more difficult). After repeated pairing, these classically conditioned environmental stimuli (e.g., contexts and objects that are frequently paired with drug use) often become drug cues which function as secondary reinforcers of drug use (i.e., once these associations are established, exposure to a paired environmental stimulus triggers a craving or desire to use the drug which they've become associated with).<ref name=pmid18654637 /><ref name="Shell vs core in addiction" />

In contrast to drugs, the release of dopamine in the NAcc shell by many types of rewarding non-drug stimuli typically undergoes habituation following repeated exposure (i.e., the amount of dopamine that is released from future exposure to a rewarding non-drug stimulus normally decreases as a result of repeated exposure to that stimulus).<ref name=pmid18654637 /><ref name="Shell vs core in addiction">Template:Cite journal</ref> Template:FOSB addiction table

Depression

In April 2007, two research teams reported on having inserted electrodes into the nucleus accumbens in order to use deep brain stimulation to treat severe depression.<ref>Brain Electrodes Help Treat Depression Template:Webarchive, Technology Review, 26 April 2007</ref> In 2010, experiments reported that deep brain stimulation of the nucleus accumbens was successful in decreasing depression symptoms in 50% of patients who did not respond to other treatments such as electroconvulsive therapy.<ref>Template:Cite journal</ref> Nucleus accumbens has also been used as a target to treat small groups of patients with therapy-refractory obsessive-compulsive disorder.<ref>Template:Cite journal</ref>

Ablation

To treat addiction and in an attempt to treat mental illness radiofrequency ablation of the nucleus accumbens has been performed. The results are inconclusive and controversial.<ref>"Controversial Surgery for Addiction Burns Away Brain's Pleasure Center" Author Maia Szalavitz. Dec. 13, 2012</ref><ref>"China Bans Irreversible Brain Procedure" Author Zamiska Nicholas. April 28, 2008. The Wall Street Journal</ref>

Placebo effect

Activation of the NAcc has been shown to occur in the anticipation of effectiveness of a drug when a user is given a placebo, indicating a contributing role of the nucleus accumbens in the placebo effect.<ref name="placebo effect" /><ref>Template:Cite journal

• Template:Cite press release</ref>

Additional images

• Dopamine and serotonin pathways.png

  Dopamine and serotonin

• Nucleus accumbens MRI.PNG

  MRI coronal slice showing nucleus accumbens outlined in red

• Nucleus accumbens sag.jpg

  Sagittal MRI slice with highlighting (red) indicating the nucleus accumbens

• Nucleus accumbens coronal sections.gif

  Nucleus accumbens highlighted in green on coronal T1 MRI images

• Nucleus accumbens sagittal sections.gif

  Nucleus accumbens highlighted in green on sagittal T1 MRI images

• Nucleus accumbens transversal sections.gif

  Nucleus accumbens highlighted in green on transversal T1 MRI images

See also

• Septal nuclei

External links

• The role of the nucleus accumbens in the reward circuit. Part of "The Brain From Top to Bottom." at thebrain.mcgill.ca
• Nucleus Accumbens – Cell Centered Database
• Template:BrainMaps