Mesolimbic Pathway

The mesolimbic pathway, often referred to as the "reward pathway," is a major dopamine pathway in the brain. This neuronal circuit is critical for motivational and reward-related behaviors, and it has also been implicated in several neuropsychiatric disorders^[1].

The mesolimbic pathway primarily originates in the ventral tegmental area (VTA), which is situated in the midbrain. From the VTA, dopaminergic neurons project to various regions, but the key destination in the context of the mesolimbic pathway is the nucleus accumbens, which is part of the ventral striatum located at the base of the forebrain^[2].

The mesolimbic pathway plays a crucial role in the processing of rewarding experiences, motivation, pleasure, and reinforcement learning. It is also involved in the perception of natural rewards, such as food and sex. It is the increased dopamine neurotransmission in this pathway from the VTA to the nucleus accumbens that leads to feelings of pleasure and reward ^[4].

In addition to these roles, the mesolimbic pathway has been implicated in the development of a number of psychiatric disorders, including addiction, schizophrenia, and depression. For example, drugs of abuse tend to increase dopamine release in this pathway, contributing to their addictive properties ^[5].

This is a simple explanation of how this works.

1. Dopamine is synthesized in the neuron from the amino acid tyrosine. Tyrosine is converted into DOPA by the enzyme tyrosine hydroxylase, and then DOPA is converted into dopamine by the enzyme DOPA decarboxylase ^[6].

2. The dopamine is then packaged into vesicles, which are tiny sac-like structures. The vesicles are bundled up in the nerve endings of the neurons, ready to be released ^[6].

3. When a rewarding event is perceived, such as eating food or engaging in sexual behaviour, the neurons in the VTA are activated. This causes an action potential, which is essentially an electrical signal, to travel down the neuron ^[7].

4. The action potential causes the vesicles to merge with the cell membrane of the neuron, releasing dopamine into the synapse. The synapse is the small space between neurons ^[8].

5. The released dopamine then binds to dopamine receptors on the neighbouring neuron in the nucleus accumbens. This is called neurotransmission ^[9].

6. This binding activates the second neuron, causing a chain reaction of neuron activation throughout the brain ^[9].

7. The brain interprets this chain reaction as a feeling of pleasure or reward, encouraging us to engage in the behaviour again. This is part of how habits form ^[10].

8. Finally, the dopamine is removed from the synapse so the signal doesn't continue indefinitely. This is done by a process called reuptake, where the dopamine is taken back into the neuron that released it. Alternatively, enzymes like monoamine oxidase (MAO) can break down the dopamine ^[6].

Increased dopamine neurotransmission in the mesolimbic pathway can lead to feelings of pleasure and reward because when more dopamine is released into the synapse and binds to the receptors on the neighbouring neuron, it amplifies the reward signal in the brain. ^[11].

The mesolimbic pathway does not work in isolation. It interacts with various other brain regions and structures:

1. Prefrontal Cortex (PFC): The VTA also sends dopaminergic projections to the PFC. This interaction is thought to play a key role in decision making, impulse control, and moderating social behaviour. Alterations in the function of this pathway have been associated with conditions like ADHD and schizophrenia ^[12].

2. Hippocampus: The hippocampus interacts with the mesolimbic pathway to process memories and contextual information about rewarding stimuli. This interaction is vital for learning associations between certain behaviors and rewards ^[13].

3. Amygdala: The amygdala, involved in emotional processing, sends input to the nucleus accumbens and can modulate the activity of the mesolimbic pathway, affecting how emotional states impact the perception of reward ^[14].

4. Hypothalamus: The hypothalamus can also influence the mesolimbic pathway, particularly in response to stress or the presence of potentially rewarding stimuli. It can either enhance or suppress the activity of the pathway, contributing to the complex regulation of motivated behaviors ^[15].