ReviewSpecificity and impact of adrenergic projections to the midbrain dopamine system

- LC and medullary NE and E neurons sends afferents to midbrain DA neurons.
- Adrenergic axons mainly form synaptic appositions indicative of a parachrine release of neurotransmitter.
- Both, α1 and α2 adrenoceptor, modulates DA neurons firing.
- NE axons are one of the sources of DA in the cortex, hippocampus and lateral habenula.
- In the absence of NE, DA neurons are more susceptible to toxicity.

Dopamine (DA) is a neuromodulator that regulates different brain circuits involved in cognitive functions, motor coordination, and emotions. Dysregulation of DA is associated with many neurological and psychiatric disorders such as Parkinson's disease and substance abuse. Several lines of research have shown that the midbrain DA system is regulated by the central adrenergic system. This review focuses on adrenergic interactions with midbrain DA neurons. It discusses the current neuroanatomy including source of adrenergic innervation, type of synapses, and adrenoceptors expression. It also discusses adrenergic regulation of DA cell activity and neurotransmitter release. Finally, it reviews several neurological and psychiatric disorders where changes in adrenergic system are associated with dysregulation of the midbrain DA system.This article is part of a Special Issue entitled SI: Noradrenergic System.