Independent presynaptic and postsynaptic mechanisms regulate endocannabinoid signaling at multiple synapses in the ventral tegmental area

Arthur C. Riegel, Carl R. Lupica

Research output: Contribution to journalArticlepeer-review

181 Scopus citations

Abstract

Dopamine (DA) neurons in the ventral tegmental area have been implicated in psychiatric disorders and drug abuse. Understanding the mechanisms through which their activity is regulated via the modulation of afferent input is imperative to understanding their roles in these conditions. Here we demonstrate that endocannabinoids liberated from DA neurons activate cannabinoid CB1 receptors located on glutamatergic axons and on GABAergic terminals targeting GABAB receptors located on these cells. Endocannabinoid release was initiated by inhibiting either presynaptic type-III metabotropic glutamate receptors or postsynaptic calcium-activated potassium channels, two conditions that also promote enhanced DA neuron excitability and bursting. Thus, activity-dependent release of endocannabinoids may act as a regulatory feedback mechanism to inhibit synaptic inputs in response to DA neuron bursting, thereby regulating firing patterns that may fine-tune DA release from afferent terminals.

Original languageEnglish (US)
Pages (from-to)11070-11078
Number of pages9
JournalJournal of Neuroscience
Volume24
Issue number49
DOIs
StatePublished - Dec 8 2004
Externally publishedYes

Keywords

  • Bursting
  • Dopamine neuron
  • GABA
  • GABA-B receptors
  • Marijuana
  • Mesolimbic
  • Metabotropic glutamate receptors
  • S channels

ASJC Scopus subject areas

  • General Neuroscience

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