Did You Know?
Several studies have established the link between nucleus accumbens and drug-induced reinforcement behavior.
The human brain is a very complex organ that guides and controls our behavior. It processes sensory information, enables us to learn, stores past events and experiences as memories, and helps us act on the basis of the processed information and/or memories. The brain is divided into hind brain, midbrain, and the forebrain, which work in tandem.
For instance, neurons in the ventral tegmental area (VTA) from the midbrain secrete a neurotransmitter called dopamine, which is involved with the neural circuits of the forebrain that are required for pleasure, reward, and attention. The axons of these neurons terminate in the nucleus accumbens (NAcc). Both the VTA and NAcc are a part of the mesolimbic dopaminergic pathway. Basically, the spontaneous firing of neurons in this region gives rise to sensations of pleasure or gratification.
The forebrain comprises several important structures such as the thalamus, hypothalamus, limbic system, and the cerebrum. The limbic system is a group of structures that plays a vital role in planning, memory, emotion, attention, and reinforcement. Basal nuclei (often referred to as basal ganglia) are clusters of nerve cells that surround the thalamus. Both basal ganglia and cerebellum communicate with the motor cortex through the thalamus. The effect of neurotransmitters from the basal ganglia and cerebellum on thalamus is inhibitory and excitatory, respectively. This balance is required for coordinated movement. The nucleus accumbens is a part of the ventral striatum of the brain.
Basal Ganglia and Nucleus Accumbens
The basal ganglia comprises a group of subcortical nuclei called striatum, subthalamic nucleus, substantia nigra pars reticulata, and globus pallidus (interna and externa). These nuclei are interconnected with the cerebral cortex, thalamus, and brainstem. The striatum, which is also referred to as the striate nucleus, is the largest nucleus of the basal ganglia. It is a striped mass of white and gray matter. It is located in each of the cerebral hemispheres, in front of the thalamus. The internal capsule divides the striatum into the caudate nucleus and the lenticular nucleus. Ventral striatum, which is a part of the striatum, comprises substantia innominata, nucleus accumbens, and the olfactory tubercle. The nucleus accumbens lies towards the front part of the preoptic area of the hypothalamus. Its ventral, medial, lateral, and dorsal borders are substantia innominata, septal area, putamen, and caudate nucleus, respectively. While the caudate, as well as putamen receive most of the input from cerebral cortex, the nucleus accumbens receives most of the input from the frontal cortex and the limbic system.
Structure and Function of Nucleus Accumbens
The nucleus accumbens is located at the meeting place of the head of the caudate and the front portion of the putamen. It is located to the side of the septum pellucidum. It is divided into two regions: core and shell. While the shell has an efferent projection to the lateral hypothalamus and the extended amygdala, such a projection does not exist in case of the core. The shell is related to the limbic system, which comprises the hippocampus, amygdala, anterior thalamic nuclei, and the limbic cortex. These are specialized structures that are involved in varied functions ranging from long-term memory, emotions, olfaction, and behavior. In fact, the limbic system is sometimes referred to as the emotional brain. While the hippocampus transfers information from the short-term memory to long-term memory, the amygdala is a part of neural circuitry associated with emotions, memory, and attention. Thus, amygdala is involved in helping us add significance to long-term memories. Hippocampus and amygdala project to the prefrontal cortex, which is a cortical region that is associated with planning and working memory. The prefrontal cortex helps us select the right behavior in a given situation, and works with the premotor cortex to initiate a particular behavior.
NAcc core comprises medium-spiny neurons with larger number of dendritic spines, branch segments, and terminal segments. The neurons from the core project to the globus pallidus and the substantia nigra. GABA is one of the main neurotransmitters in the NAcc region. Majority of the neurons are medium-spiny GABA-ergic projection neurons, but large cholinergic interneurons are also present. The neurons receive input from the dopaminergic neurons of the ventral tegmental area (VTA) and the glutamatergic neurons of the hippocampus, amygdala, and medial prefrontal cortex. On being activated by these inputs, the projections of the medium-spiny neurons release GABA on to the ventral pallidum.
The Role of Nucleus Accumbens in Addiction
Nucleus accumbens is a part of the mesolimbic pathway, which is a dopaminergic pathway that starts in the ventral tegmental area of the midbrain and connects to the nucleus accumbens. This VTA-NAcc neural circuit is associated with the release of dopamine, which in turn is believed to play a vital role in the experience of pleasure and reward. It is also linked to compulsive drug-seeking behavior, loss of control, or inability of the drug addicts to stop themselves in spite of being aware of the ill-effects. This behavior has been linked to increased dopamine transmission in the limbic system. Studies have shown an increase in dopamine release in NAcc in case of drug addicts while they abuse opiates, nicotine, ethanol, and psychostimulants. Activity in this region has also been observed while participating in rewarding experiences related to food, music, sex, etc. Dopamine transmission has also been implicated in schizophrenia and depression.
Let's understand the importance of the mesolimbic pathway, which is also referred to as the reward pathway of the brain. It is the mesolimbic pathway that is involved in inducing pleasurable sensations when we eat, drink, or engage in certain types of behavior. The reward pathway connects to several areas of the brain. The ventral tegmental area is the site of dopaminergic neurons. VTA creates the awareness of a rewarding stimulus (natural reward such as food, drinks, sex, or even the use of drugs of abuse such as cocaine). NAcc is the target of VTA dopamine neurons, and is involved in mediating pleasure or the rewarding effects of the stimulus. Even the amygdala interacts with the VTA and NAcc, and helps in determining the rewarding or aversive nature of the stimulus. Together, the hippocampus and the amydala create memories of such experiences. This neural circuit is also responsible for reinforcing behavior.
While the senses collect information from the environment and send signals to the brain about the presence of a stimulus, the memories established by the hippocampus and the amygdala remind us of the experience. Thereafter, the brain sends signals to the other parts of the body to indulge in such a behavior. As a result, neurons in the reward pathway release dopamine, which provides the sensation of pleasure. Thus, the reward pathway connects to the regions of the brain that control memory and behavior, thereby making us repeat the behavior in the presence of that stimulus.
On a concluding note, nucleus accumbens is integral to the experience of pleasure in case of natural stimuli such as food or sexual behavior, or even the use of recreational drugs or alcohol. Being the target of addictive drugs, it is often implicated in drug addiction. Animal studies have also linked increased dopamine increase in this region to maternal behavior. In fact, deep brain stimulation of this area has been found to be beneficial in the treatment of depression in patients who didn't respond to electroconvulsive therapy.