Dopamine

Dopamine is a catecholamine neurotransmitter synthesized from the amino acid tyrosine. It is produced by neurons in several specific brain regions, most prominently the ventral tegmental area (VTA) and substantia nigra, which project to the striatum (including the nucleus accumbens), prefrontal cortex, limbic system, and other regions.

Dopamine has multiple functions depending on the circuit in which it operates. In the mesolimbic pathway (VTA to nucleus accumbens), dopamine encodes reward prediction signals — it fires not simply in response to rewards but to prediction errors, signaling when outcomes are better or worse than expected. This makes dopamine central to motivation, reinforcement learning, and goal-directed behavior. In the mesocortical pathway (VTA to prefrontal cortex), dopamine modulates working memory and executive function. In the nigrostriatal pathway (substantia nigra to striatum), dopamine controls voluntary movement.

Dopamine is synthesized from L-DOPA (levodopa) by aromatic amino acid decarboxylase, and is degraded by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). These enzymes are targets for several important drugs — MAO inhibitors and L-DOPA are among the most important treatments for Parkinson's disease.

Prefrontal dopamine is critical for working memory. The 'inverted-U' relationship between dopamine and prefrontal function means there is an optimal level — too little or too much dopamine both impair working memory and executive function. This is one reason why stress (which depletes prefrontal dopamine) and stimulant drugs (which flood dopamine receptors) both impair executive function despite having opposite effects on dopamine levels.

Dopamine neurons in the substantia nigra are the cells selectively destroyed in Parkinson's disease, causing the movement symptoms characteristic of the condition. Cognitive impairment in Parkinson's is substantially mediated by dopamine loss in prefrontal circuits. In Alzheimer's disease, dopaminergic changes occur later but contribute to motivational and behavioral symptoms.

Dopamine is central to the experience of motivation and reward. Decline in dopaminergic function with aging — dopamine receptor density falls approximately 10% per decade from early adulthood — contributes to age-related changes in motivation, reward sensitivity, and the subjective experience of pleasure. These changes may also contribute to increased susceptibility to depression in older adults.