Cannabinoids Enhance Subsecond Dopamine Release in the Nucleus Accumbens of Awake Rats

Joseph F. Cheer, Kate M. Wassum, Michael L.A.V. Heien, Paul E.M. Phillips, R. Mark Wightman

Research output: Contribution to journalArticle

233 Scopus citations

Abstract

Dopaminergic neurotransmission has been highly implicated in the reinforcing properties of many substances of abuse, including marijuana. Cannabinoids activate ventral tegmental area dopaminergic neurons, the main ascending projections of the mesocorticolimbic dopamine system, and change their spiking pattern by increasing the number of impulses in a burst and elevating the frequency of bursts. Although they also increase time-averaged striatal dopamine levels for extended periods of time, little is known about the temporal structure of this change. To elucidate this, fast-scan cyclic voltammetry was used to monitor extracellular dopamine in the nucleus accumbens of freely moving rats with subsecond timescale resolution. Intravenous administration of the central cannabinoid (CB1) receptor agonist, R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1, 4-benzoxazin-6-yl]-(1-naphthalenyl) methanone mesylate, dose-dependently produced catalepsy, decreased locomotion, and reduced the amplitude of electrically evoked dopamine release while markedly increasing the frequency of detected (nonstimulated) dopamine concentration transients. The CB1 receptor antagonist [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl) -4-methylpyrazole-3-carboxamide] reversed and prevented all agonist-induced effects but did not show effects on dopamine release when injected alone. These data demonstrate that doses of a cannabinoid agonist known to increase burst firing produce ongoing fluctuations in extracellular dopamine on a previously unrecognized temporal scale in the nucleus accumbens.

Original languageEnglish (US)
Pages (from-to)4393-4400
Number of pages8
JournalJournal of Neuroscience
Volume24
Issue number18
DOIs
StatePublished - May 5 2004
Externally publishedYes

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Keywords

  • Accumbens
  • Cannabinoids
  • Cyclic voltammetry
  • Dopamine
  • Drug abuse
  • Neuromodulation

ASJC Scopus subject areas

  • Neuroscience(all)

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