background Fear acquisition and extinction have an important role in the development and treatment of anxiety disorders.
aim To review the neurobiological mechanisms of fear acquisition and extinction, with emphasis on preclinical research and focussing on the glutamatergic system.
method Both recent literature as well as historic articles were studied.
results First described by Aristotle in his law of contiguity, which states that things which occur in proximity to each other in time or space are readily associated, it was Pavlov who started a revolution in science at the start of last century when he unravelled the basics of this type of learning: classical conditioning.
From the 1960s on, Nobel laureate Eric Kandel, using a reductionist approach, unravelled the neurobiological mechanisms underlying longterm potentiation in the large sea snails, Aplysia. Consolidation of conditioned fear was found to rely on structural intracellular changes that result from a cascade of second messengers leading to promotion and blocking of nuclear transcription of proteins.
conclusion This historic overview is necessary to understand the rationale for targeting the glutamate system in the treatment of anxiety disorders in recent human studies.