Role of endogenous acetylcholine in the control of the dopaminergic system via nicotinic receptors

J Neurochem. 2010 Aug;114(3):641-6. doi: 10.1111/j.1471-4159.2010.06798.x. Epub 2010 May 4.

Abstract

Nicotinic acetylcholine receptors (nAChRs) are pentameric membrane protein receptors activated by the addictive drug, nicotine. However, sometimes underestimated, under physiological conditions the endogenous neurotransmitter acetylcholine is the agonist. In this mini-review, I will discuss the evidence in favour of an important role for this cholinergic activation of the dopaminergic (DAergic) system. I will focus on the literature implicating the action of acetylcholine on the somato-dendritic compartment of these neurons. This modulation is responsible for a variety of phenotypes in knock-out animals of nAChR subunits. These include locomotion, exploratory behaviour, dopamine (DA) release, and DA neuron firing patterns. The novel techniques brought to bear on these analyses, lentiviral re-expression, and repression, of nAChR subunits, and transgenic expression of hypersensitive receptors will be discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylcholine / chemistry
  • Acetylcholine / physiology*
  • Animals
  • Brain / metabolism
  • Brain / physiology
  • Dopamine / metabolism
  • Dopamine / physiology*
  • Humans
  • Neurons / drug effects
  • Neurons / metabolism*
  • Nicotine / pharmacology
  • Receptors, Nicotinic / biosynthesis
  • Receptors, Nicotinic / drug effects
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / physiology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology

Substances

  • Receptors, Nicotinic
  • Nicotine
  • Acetylcholine
  • Dopamine