Nucleus Accumbens

The Nucleus Accumbens, represented by NAc or NAcc is also known as accumbens nucleus. It is a part of basal ganglia. The nucleus is relatively a very small structure in brain but performs a variety of functions.

The functions of this nucleus range from controlling the reward and punishment centers of the brain to playing an important role in multiple psychotic problems such as addiction, depression, and ablation.

In this article, we will study the anatomical characteristics of nucleus accumbens along with its important neurotransmitters and its role in a number of psychotic illnesses.

Anatomical Features

Under this heading, we will discuss important
anatomical features such as input and output pathways, and parts of the nucleus
accumbens. We also discuss the types of neurons present in this nucleus.

Location in Brain

The Nucleus Accumbens is present in the basal region of the forebrain. It is a part of the basal ganglia. The nucleus accumbens is an important part of the ventral striatum. This ventral striatum along with the dorsal striatum form the striatum of basal ganglia, the most important structure of basal ganglia.

Structure

The structure of the nucleus accumbens comprises a shell and a core.

Shell

It is also known as nucleus accumbens shell or NAcc
shell. It is a substructure of nucleus accumbens. It is present in the outer
region of the nucleus accumbens. It is also referred to as a part of dorsal
amygdala.

Core

It is also called nucleus accumbens core or NAcc core.
It is present in the inner region of the nucleus accumbens. It is considered to
be the part of ventral striatum of the basal ganglia.

Afferent Fibers

The nucleus accumbens receives glutaminergic, dopaminergic and histaminergic input fibers from different areas of the brain.

The major glutaminergic fibers are received from the prefrontal cortex, basolateral part of the amygdala, midline and intralaminar nuclei of thalamus, and ventral hippocampus. The glutaminergic fibers are also received from the ventral tegmental area.

The major dopaminergic fibers to the nucleus accumbens
come from the ventral tegmental area of the midbrain.

The other important input fibers to the nucleus
accumbens are the histaminergic fibers. These fibers are received from the
tuberomammillary nucleus. This nucleus is the only source of histamine in the brain.

Efferent Fibers

These are the output fibers of the nucleus accumbens. The nucleus accumbens send output fibers to the basal ganglia and globus pallidus. The globus pallidus, in turn, sends output fibers to the medial dorsal nucleus of the thalamus which then project back to striatum as well as to the prefrontal cortex.

The nucleus accumbens also sends efferent fibers to
the ventral tegmental area, substantia nigra and the reticular formation
present in the pons.

Cells

Most of the cells present in the nucleus accumbens are the GABA secreting cells, the GABAergic neurons. They are called the medium spiny neurons or MSNs. These cells express Dopamine D1 or D2 receptors on their cell membranes.

The GABAergic neurons present in the core of the
nucleus accumbens are known to have dendritic spines.

Other cells that are present in the nucleus accumbens
include interneurons, that may be cholinergic or GABAergic in nature.

Neurotransmitters and their Receptors

Neurotransmitters are the key functional molecules that help nucleus accumbens perform its functions. Any disturbance in the normal balance of these neurotransmitters can lead to a number of psychotic illnesses. In this section, we will discuss the important neurotransmitters in the nucleus accumbens one by one.

Dopamine

Dopamine is released by the dopaminergic input fibers in the nucleus accumbens in response to a rewarding stimulus. It may also be released in response to the consumption of recreational drugs such as morphine, acetaminophen, cocaine, and nicotine. This dopamine in the nucleus accumbens is responsible for drug addiction.

Serotonin

Serotonin is another important neurotransmitter in the nucleus accumbens. A large number of synapses are present in the nucleus accumbens that use serotonin as a neurotransmitter.it is also believed to be associated with the addiction process.

GABA

GABA receptors are present in the cell membranes of the neurons making the shell of nucleus accumbens. The stimulation of these receptors by GABA_A agonists has an inhibitory role in changing the behavior of the person influenced by dopamine. Thus, GABA has a role in withdrawal and treatment of addiction.

Glucocorticoids

The glucocorticoid receptors are also present on the
neurons making the shell of nucleus accumbens. Studies have shown that the
suppression of these glucocorticoid receptors by using glucocorticoid
antagonists have decreased the release of dopamine.

Glutamate

The NMDA glutamate receptors are present on the neurons making the core of the nucleus accumbens. These receptors are essential for the process of spatial and instrumental learning. The blockade of these receptors has been shown to impair spatial learning in various studies.

Functions of Nucleus Accumbens

The important functions performed by the nucleus
accumbens include the following:

Reward and Reinforcement

The nucleus accumbens is a part of the reward system of our brain. It plays an important role in the analysis and processing of the reward and reinforcing stimuli.

A rewarding stimulus is an external stimulus that is perceived by the brain as intrinsically positive and desirable.

A reinforcing stimulus is an external stimulus that
causes the repeating behavior paired with the stimulus.

The neurons in the nucleus accumbens are related to
pleasure experience. It causes the pleasure and reward a person feels after
engaging in sexual intercourse. The same pleasure and reward response generated
by the nucleus accumbens is responsible for the addictive behavior towards sex
and recreational drugs.

The pleasure or reward response is due to the release of dopamine in the nucleus accumbens. The dopaminergic fibers from the ventral tegmental area upon activation release the dopamine in the nucleus accumbens. This dopamine causes activation of D1 receptors, generating a reward response.

Aversive Behavior

The nucleus accumbens also plays a role in aversion from a stimulus. An aversion stimulus is an unpleasant stimulus that causes behavioral changes via negative enforcement and positive punishment.

The activation of D2 receptors in the nucleus
accumbens is responsible for the aversive behavior.

Sleep

The nucleus accumbens is also involved in the regulation of slow-wave sleep. There are special adenosine A_2A receptors present in the neurons of the core of the nucleus. The activation of these receptors has been shown to induce the slow-wave sleep.

The inhibition of these adenosine receptors was found associated with the suppression of sleep.

Clinical Significance

The nucleus accumbens is significant in the following
clinical conditions:

Addiction

The nucleus accumbens is the most important part of the mesolimbic system that is associated with addiction. As we have described in the Reward and Reinforcement section, nucleus accumbens is responsible for the rewarding response towards a rewarding and reinforcing stimulus.

It is due to the release of dopamine that stimulates D1 receptors in the nucleus accumbens.

The addiction to the abusive drugs is due to this dopamine phenomenon. The drugs such as amphetamines, cocaine, morphine, etc. increase the dopamine levels in the nucleus accumbens. This causes a reinforcing and addictive behavior toward the drug.

Depression

The stimulation of neurons in the nucleus accumbens has been effective in the treatment of depression. It has been shown to decrease depression symptoms in 50% of the patients who did not respond to other therapeutic techniques.

The stimulation of the same neurons is also used as a
therapeutic technique in patients of OCD.

Placebo Effect

 When a person
is given a placebo drug, there is activation of neurons in the nucleus
accumbens. This indicates that the nucleus accumbens plays an important role in
the placebo effect.

Conclusion/Summary

The nucleus accumbens referred to as NAc or NAcc is a small nucleus present in the basal ganglia of forebrain. 

It consists of an outer shell, which is a part of the dorsal
amygdala, and an inner core, a part of ventral striatum of the basal ganglia.

The nucleus accumbens receives glutaminergic,
dopaminergic and histaminergic input fibers from different areas of the brain.

The important output fibers are sent to the globus
pallidus and substantia nigra, ventral tegmental area, and reticular formation
in pons.

Most of the cells in the nucleus are GABAergic,
although some cholinergic interneurons are also present.

The important neurotransmitters that influence the activity of the nucleus accumbens include:

• Dopamine
• Glutamate
• GABA
• Serotonin
• Glucocorticoids

The most important function of nucleus accumbens is to process and analyze the rewarding and reinforcing stimuli. It also plays a role in aversive behavior and regulation of sleep. It is also important in spatial and instrumental learning.

Addiction is the major clinical condition associated
with the nucleus accumbens. It is also important in the placebo effect and
treatment of depression.

References

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