Nicotine Enhancement of Dopamine Release by a Calcium-Dependent Increase in the Size of the Readily Releasable Pool of Synaptic Vesicles

A major factor underlying compulsive tobacco use is nicotine-induced modulation of dopamine release in the mesolimbic reward pathway (Wise and Rompre, 1989). An established biochemical mechanism for nicotine-enhanced dopamine release is by activating presynaptic nicotinic acetylcholine receptors (nAChRs) (Wonnacott, 1997). Prolonged application of 10-7 to 10-5 m nicotine to striatal synaptosomes promoted a sustained efflux of [3H]dopamine. This nicotine effect was mediated by non-α7 nAChRs, because it was blocked by 5 μm mecamylamine but was resistant to 100 nm α-bungarotoxin (αBgTx). Dopamine release was diminished by omitting Na+ or by applying peptide calcium channel blockers, indicating that nAChRs trigger release by depolarizing the nerve terminals. However, because α7 receptors rapidly desensitize in the continuous presence of agonists, a repetitive stimulation protocol was used to evaluate the possible significance of desensitization. This protocol produced a transient increase in [3H]dopamine released by depolarization and a significant increase in the response to hypertonic solutions that measure the size of the readily releasable pool (RRP) of synaptic vesicles. The nicotine-induced increase in the size of the readily releasable pool was blocked by αBgTx and by the calmodulin antagonist calmidazolium, suggesting that Ca2+ entry through α7 nAChRs specifically enhances synaptic vesicle mobilization at dopamine terminals. Thus, nicotine enhances dopamine release by two complementary actions mediated by discrete nAChR subtypes and suggest that the α7 nAChR-mediated pathway is tightly and specifically coupled to refilling of the RRP of vesicles in dopamine terminals.

• Publication year

  2004

• Venue

  Journal of Neuroscience

• Publication date

  2004-12-15

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1523/JNEUROSCI.1559-04.2004PMID 15601939PMCID PMC6730353
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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