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Nucleus accumbens

Nucleus accumbens
Medial surface, person facing to the left. Nucleus accumbens is very roughly in Brodmann area 34
Latin nucleus accumbens septi
Part of Mesolimbic pathway
Basal ganglia (Ventral striatum)
Components Nucleus accumbens shell
Nucleus accumbens core
Acronym(s) NAc or NAcc
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Anatomical terms of neuroanatomy

The nucleus accumbens (NAc or NAcc), also known as the accumbens nucleus or 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.[1] The nucleus accumbens and the olfactory tubercle collectively form the ventral striatum, which is part of the basal ganglia.[2]

The nucleus accumbens has a significant role in the cognitive processing of motivation, pleasure, and reward and reinforcement learning, and hence has significant role in addiction.[3][4] It plays a lesser role in fear, impulsivity, and the placebo effect.[5][6][7] It is involved in the encoding of new motor programs as well.[3]

Each cerebral hemisphere has its own nucleus accumbens. It is located where the head of the caudate and the anterior portion of the putamen meet just lateral to the septum pellucidum. The nucleus accumbens can be divided into two structures—the nucleus accumbens core and the nucleus accumbens shell. These structures have different morphology and function.


The nucleus accumbens is an aggregate of neurons which is described as having an outer shell and an inner core.[3]


Major inputs to the nucleus accumbens include the prefrontal cortex, basolateral amygdala, and dopaminergic neurons located in the ventral tegmental area (VTA), which connect via the mesolimbic pathway. Thus the nucleus accumbens is often described as one part of a cortico-striato-thalamo-cortical loop.

Dopaminergic input from the VTA modulate the activity of 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.).[8][9]

Another major source of input comes from the CA1 and ventral subiculum of the hippocampus to the dorsomedial area of the nucleus accumbens. The neurons of the hippocampus have a noteworthy correlation to slight depolarizations of cells in the nucleus accumbens, which makes them more positive and therefore 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.[10]

The nucleus accumbens is one of the few regions that receive histaminergic projections from the tuberomammillary nucleus (the sole source of histamine neurons in the brain).[11]


The output neurons of the nucleus accumbens send axon 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 the striatum. Other efferents from the nucleus accumbens include connections with the tail of the ventral tegmental area,[12] substantia nigra, and the reticular formation of the pons.[1]


The nucleus accumbens 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. 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.[13][14][15]

Function: The shell of the nucleus accumbens is involved in the cognitive processing of motivational salience (wanting) as well as reward and reinforcement effects.[3] Particularly important are the effects of drug and naturally rewarding stimuli on the NAc shell because these effects are related to addiction.[3] Addictive drugs have a larger effect on dopamine release in the shell than in the core.[3]


The nucleus accumbens 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. 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.[13][15]

Function: The nucleus accumbens core is involved in the cognitive processing of motor function related to reward and reinforcement.[3] Specifically, the core encodes new motor programs which facilitate the acquisition of a given reward in the future.[3]

Cell types

The core of the NAcc is made up mainly of medium spiny neurons. Compared to the neurons 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.[13][15] These neurons are also the main projection or output neurons of the nucleus accumbens.

Approximately 95% of neurons in the nucleus accumbens are GABAergic medium spiny neurons which primarily express either D1-type or D2-type receptors;[8] About 1–2% of the remaining neuronal types are large aspiny cholinergic interneurons and another 1–2% are GABAergic interneurons.[8]


Dopamine: Dopamine is related to recreational drugs including amphetamines, cocaine, and morphine, which increase extracellular levels of dopamine in both the NAc shell and the NAc core, but the effect of these increases is more pronounced in the shell. Only amphetamine at high levels increases extracellular levels of dopamine to similar levels in both the shell and the core. All of this points to a 'functional heterogeneity' in the nucleus accumbens between the shell region and the core region.[16] Similarly to drug rewards, non-drug rewards also increase levels of extracellular dopamine in the NAc shell, but drug induced DA increase is more resilient to habituation when exposed repeatedly to drug-stimuli, unlike non-drug rewarding stimuli induced dopamine increases, which do succumb to habituation. Recent[when?] studies have shown that the repeated influence of drug-inducing DA projection has an abnormal strengthening effect on stimulus-drug associations and increases the drug-reward stimuli’s resistance to extinction. This may be a contributing factor to addiction. This effect was more pronounced in the NAc shell than in the NAc core.[13][17]

Phenethylamine and tyramine: Phenethylamine and tyramine are trace amine compounds which are synthesized in several types of CNS neurons, including all dopamine neurons.[18] Specifically, these neurotransmitters act within the dopaminergic inputs to the NAcc. These substances regulate the presynaptic release of dopamine through their interactions with VMAT2 and TAAR1, analogous to amphetamine.

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 regards 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.[19]

GABA: A recent study on rats that used GABA agonists and antagonists indicated that GABAA receptors in the NAc shell have inhibitory control on turning behavior influenced by dopamine, and GABAB receptors have inhibitory control over turning behavior mediated by acetylcholine.[13][20]

Glutamate: Studies have shown that local blockade of glutamatergic NMDA receptors in the NAcc core impaired spatial learning.[21] Another study demonstrated that both NMDA and AMPA (both glutamate receptors) play important roles in regulating instrumental learning.[22]

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


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).[3][23] The nucleus accumbens is selectively activated during the perception of pleasant, emotionally arousing pictures and during mental imagery of pleasant, emotional scenes.[24][25] A 2005 study found that it is involved in the regulation of emotions induced by music,[26] perhaps consequent to its role in mediating dopamine release. The nucleus accumbens plays a role in rhythmic timing and is considered to be of central importance to the limbic-motor interface (Mogensen).[citation needed]

In the 1950s, James Olds and Peter Milner implanted electrodes into the septal area of the rat and found that the rat chose to press a lever which stimulated it. It continued to prefer this even over stopping to eat or drink. This suggests that the area is the "pleasure center" of the brain and is involved in reinforcement learning.[27] In rats, stimulation of the ventral tegmental area causes the release of dopamine in the nucleus accumbens much in the same way as addictive drugs and natural reinforcers, such as water or food, initiate the release of dopamine in the nucleus accumbens.[28] The same results have been seen in human subjects in functional imaging studies. For example, increased dopamine concentration is seen in the extracellular fluid of the nucleus accumbens when subjects believed they were being given money[citation needed], and increased activation (i.e., increased fMRI BOLD signal-change) was observed among heterosexual males viewing pictures of attractive women.[29]

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.[30] Levels of dopamine increase in the nucleus accumbens during maternal behavior, while lesions in this area upset maternal behavior.[31] 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".[32]

Clinical significance


Current models of addiction from chronic drug use involve alterations in gene expression in the mesocorticolimbic projection.[8][33][34] 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).[8] 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 seen in drug addiction;[8] it has been implicated in addictions to alcohol, cannabinoids, cocaine, nicotine, phenylcyclidine, opiates, and substituted amphetamines.[8][33][35] ΔJunD is the transcription factor which directly opposes ΔFosB.[8] 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).[8]

ΔFosB also plays an important role in regulating behavioral responses to natural rewards, such as palatable food, sex, and exercise.[8][9] 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.[8][9][23] Consequently, ΔFosB is the key transcription factor involved in addictions to natural rewards as well;[8][9][23] in particular, ΔFosB in the nucleus accumbens is critical for the reinforcing effects of sexual reward.[9] 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.[23][36]

Summary of addiction-related plasticity
Form of neural or behavioral plasticity Type of reinforcer Sources
Opiates Psycho­stimulants High fat or sugar food Sexual reward Physical exercise
ΔFosB expression in
nucleus accumbens D1-type MSNs
Behavioral plasticity
Escalation of intake Yes Yes Yes [23]
Yes Not applicable Yes Yes Attenuated Attenuated [23]
conditioned place preference
Reinstatement of drug-seeking behavior [23]
Neurochemical plasticity
CREB phosphorylation
in the nucleus accumbens
Sensitized dopamine response
in the nucleus accumbens
No Yes No Yes [23]
Altered striatal dopamine signaling DRD2, ↑DRD3 DRD1, ↓DRD2, ↑DRD3 DRD1, ↓DRD2, ↑DRD3 DRD2 DRD2 [23]
Altered striatal opioid signaling μ-opioid receptors μ-opioid receptors
κ-opioid receptors
μ-opioid receptors μ-opioid receptors No change No change [23]
Changes in striatal opioid peptides dynorphin dynorphin enkephalin dynorphin dynorphin [23]
Mesocorticolimbic synaptic plasticity
Number of dendrites in the nucleus accumbens [23]
Dendritic spine density in
the nucleus accumbens
No change [23]


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.[37] 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.[38] Nucleus accumbens has also been used as a target to treat small groups of patients with therapy-refractory obsessive-compulsive disorder.[39]

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.[6][40]

Additional images


  1. ^ a b Carlson, Neil R. Physiology of Behavior. 11th ed. Boston: Pearson, 2013. Print.[page needed]
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    The brain reward circuitry that is targeted by addictive drugs normally mediates the pleasure and strengthening of behaviors associated with natural reinforcers, such as food, water, and sexual contact. Dopamine neurons in the VTA are activated by food and water, and dopamine release in the NAc is stimulated by the presence of natural reinforcers, such as food, water, or a sexual partner. ...
    The NAc and VTA are central components of the circuitry underlying reward and memory of reward. As previously mentioned, the activity of dopaminergic neurons in the VTA appears to be linked to reward prediction. The NAc is involved in learning associated with reinforcement and the modulation of motoric responses to stimuli that satisfy internal homeostatic needs. The shell of the NAc appears to be particularly important to initial drug actions within reward circuitry; addictive drugs appear to have a greater effect on dopamine release in the shell than in the core of the NAc.
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  9. ^ a b c d e Blum, Kenneth; Werner, Tonia; Carnes, Stefanie; Carnes, Patrick; Bowirrat, Abdalla; Giordano, John; Marlene-Oscar-Berman; Gold, Mark (2012). "Sex, Drugs, and Rock 'N' Roll: Hypothesizing Common Mesolimbic Activation as a Function of Reward Gene Polymorphisms". Journal of Psychoactive Drugs 44 (1): 38–55. PMC 4040958. PMID 22641964. doi:10.1080/02791072.2012.662112. It has been found that deltaFosB gene in the NAc is critical for reinforcing effects of sexual reward. Pitchers and colleagues (2010) reported that sexual experience was shown to cause DeltaFosB accumulation in several limbic brain regions including the NAc, medial pre-frontal cortex, VTA, caudate, and putamen, but not the medial preoptic nucleus. Next, the induction of c-Fos, a downstream (repressed) target of DeltaFosB, was measured in sexually experienced and naive animals. The number of mating-induced c-Fos-IR cells was significantly decreased in sexually experienced animals compared to sexually naive controls. Finally, DeltaFosB levels and its activity in the NAc were manipulated using viral-mediated gene transfer to study its potential role in mediating sexual experience and experience-induced facilitation of sexual performance. Animals with DeltaFosB overexpression displayed enhanced facilitation of sexual performance with sexual experience relative to controls. In contrast, the expression of DeltaJunD, a dominant-negative binding partner of DeltaFosB, attenuated sexual experience-induced facilitation of sexual performance, and stunted long-term maintenance of facilitation compared to DeltaFosB overexpressing group. Together, these findings support a critical role for DeltaFosB expression in the NAc in the reinforcing effects of sexual behavior and sexual experience-induced facilitation of sexual performance. ... both drug addiction and sexual addiction represent pathological forms of neuroplasticity along with the emergence of aberrant behaviors involving a cascade of neurochemical changes mainly in the brain's rewarding circuitry. 
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    Table 1
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