Dopamine Pharmacodynamics: New Insights

Abstract

Dopamine is a key neurotransmitter involved in physiological processes such as motor control, motivation, reward, cognitive function, and maternal and reproductive behaviors. Therefore, dysfunctions of the dopaminergic system are related to a plethora of human diseases. Dopamine, via different circuitries implicated in compulsive behavior, reward, and habit formation, also represents a key player in substance use disorder and the formation and perpetuation of mechanisms leading to addiction. Here, we propose dopamine as a model not only of neurotransmission but also of neuromodulation capable of modifying neuronal architecture. Abuse of substances like methamphetamine, cocaine, and alcohol and their consumption over time can induce changes in neuronal activities. These modifications lead to synaptic plasticity and finally to morphological and functional changes, starting from maladaptive neuro-modulation and ending in neurodegeneration.

Keywords: addiction; dopamine; neuromodulation; neurotoxicity; reward system.

Figure 1

The dopaminergic system can be both activated and hypoactivated in different pathological conditions. In some diseases such as schizophrenia, dopaminergic action can be upregulated or downregulated depending on the brain area considered.

Figure 2

The effect of dopamine is not only receptorial but also extra-receptorial and is in turn regulated by numerous factors.

Figure 3

Substances of abuse activate the dopaminergic system in a different way and with a different intensity. This difference is inherent in their different mechanisms of action of substances of abuse. For example, palatable substances also activate the reward circuit through gustatory stimulation.