Dopamine

Dopamine is a neurotransmitter produced in the brain that plays critical roles in reward-driven behaviour, motor control, motivation, learning, and mood regulation^[1].

Dopamine is primarily produced in two regions of the brain: the substantia nigra and the ventral tegmental area. These regions are part of the basal ganglia, a collection of neurons involved in functions including motor control and reward^[2].

The synthesis of dopamine begins with the amino acid tyrosine. The enzyme tyrosine hydroxylase converts tyrosine into L-DOPA (levodopa), and then L-DOPA is converted into dopamine by the enzyme DOPA decarboxylase (also known as aromatic L-amino acid decarboxylase). Once synthesised, dopamine is stored in small, bubble-like compartments in the neuron called vesicles, from where it is released into the synaptic cleft (the tiny gap between neurons) in response to certain stimuli^[3].

On the other side of the synapse, other neurons have receptors that dopamine binds to, which triggers a change in the receiving neuron. Receptors that bind to dopamine are a class of G protein-coupled receptors known as dopamine receptors^[5].

There are five known subtypes of dopamine receptors, grouped into two main families^[6]:

1. D1-like family:

• D1 receptors (DRD1): D1 receptors are the most abundant dopamine receptor in the CNS. When activated, they stimulate the production of cyclic AMP (cAMP) via the activation of adenylate cyclase. They're mostly found in the striatum, limbic areas, and the cortex, and are associated with cognitive processing, motivation, mood, and the regulation of voluntary movement^[7].

• D5 receptors (DRD5): D5 receptors are less abundant but have a similar mechanism of action to D1 receptors – stimulating cAMP production. They're largely expressed in the hippocampus, hypothalamus, and cortex. D5 receptors also play a role in the regulation of mood and cognition, but they are less understood than D1 receptors^[8].

2. D2-like family:

• D2 receptors (DRD2): D2 receptors, when activated, inhibit the production of cAMP by inhibiting adenylate cyclase. They're expressed in the striatum, limbic areas, and the pituitary gland. They're associated with pleasure, reward, and reinforcement learning, as well as movement and endocrine control. There are two isoforms of this receptor, D2S (short) and D2L (long), which have slightly different functions and are produced from the same gene through alternative splicing^[9].

• D3 receptors (DRD3): D3 receptors are similar to D2 receptors in their inhibitory effect on cAMP production. However, they have a more limited distribution, mainly in the limbic areas, which suggests a role in the regulation of mood and reward^[10].

• D4 receptors (DRD4): D4 receptors also inhibit cAMP production. They are less abundant and have a more scattered distribution throughout the brain, including the frontal cortex and midbrain regions. Variations in the DRD4 gene have been associated with novelty-seeking behaviour and attention deficit hyperactivity disorder (ADHD)^[11].

The different dopamine receptors, while they all bind dopamine, have unique distributions in the brain and interact with intracellular signalling pathways in different ways, which leads to their involvement in a wide array of physiological functions^[12].

Functionally, dopamine plays critical roles in various brain functions:

1. Reward and pleasure: Dopamine is often called the "feel-good" neurotransmitter because it is intimately involved in reward and pleasure mechanisms. When you experience something pleasurable, your brain often releases dopamine, which reinforces the desire to repeat the behaviour^[14].

2. Motor control: Dopamine is also crucial for coordinating smooth and controlled movements. This is demonstrated in conditions such as Parkinson's disease where there is a loss of dopamine-producing cells, leading to motor symptoms such as tremors, rigidity, and bradykinesia. Dopamine is also implicated in speaking conditions such as Tourette's, stuttering, and apraxia^[15].

3. Motivation and drive: Dopamine is linked to motivation and the feeling of being focused and energised. Higher levels of dopamine tend to result in people feeling more motivated and energised, whereas lower levels are associated with lethargy and a lack of motivation^[16].

4. Learning and memory: Dopamine is also important for learning and memory, especially in relation to reinforcement learning, where it contributes to the "reward prediction error" signal used to update our expectations and decisions^[17].

5. Regulation of mood: Dopamine plays a role in the regulation of mood and emotional responses. Imbalances in dopamine levels can lead to mood disorders such as depression and bipolar disorder^[18].

6. Neuroplasticity: the release of dopamine during rewarding experiences helps to strengthen neural connections, making it easier for those neural pathways to be activated in the future^[19].

Dopamine is often associated with pleasure and reward, but its role is a bit more nuanced. Research over the past few decades suggests that dopamine's primary function is not necessarily to make us 'feel good', but rather to motivate us to seek rewards and anticipate them^[21].

Dopamine neurons in the brain seem to become activated, or "fire," when a reward is greater than expected - a phenomenon called "prediction error." This is a crucial element of reinforcement learning, a type of learning in which an individual learns to perform certain behaviours in anticipation of a reward^[22].

For example, if you find a $20 bill on the street unexpectedly, your brain's dopamine system would register a positive prediction error and release dopamine. This release helps encode the event and its context, promoting future behaviours to seek out similar rewards (like paying more attention to the ground while walking)^[23].

However, if you were expecting to find $20 and you did, dopamine neurons wouldn't fire to the same extent because the reward matched the expectation - there is no prediction error. If you were expecting to find $20 and found nothing, a negative prediction error would be registered, potentially leading to feelings of disappointment^[24].

Over time, dopamine also appears to play a critical role in associating specific cues or contexts with potential rewards. If a cue consistently predicts a reward, the dopamine "spike" shifts to the cue rather than the reward itself. This is why just the smell of your favourite food or the intro music to a beloved TV show can evoke a strong sense of anticipation^[25].

P.S. Dopamine is arguably the most fascinating neurotransmitter in the brain, and if you would like to know more about its influences on behaviour, along with hormones, early development, and a wealth of other factors and have 30-60 hours to spare, this author highly recommends neuroendocrinologist Robert Sapolsky's Stanford lectures on YouTube, or his book Behave.