Neurochemical evidence that stimulation of CB1 cannabinoid receptors on GABAergic nerve terminals activates the dopaminergic reward system by increasing dopamine release in the rat nucleus accumbens

Beáta Sperlágh, Katalin Windisch, Rómeó D. Andó, E. Sylvester Vizi

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

We examined the effect of cannabinoid receptor activation on basal and electrical field simulation-evoked (25 V, 2 Hz, 240 shocks) [3H]dopamine efflux in the isolated rat nucleus accumbens in a preparation, in which any effect on the dendrites or somata of ventral tegmental projection neurons was excluded. The cannabinoid agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate (WIN55,212-2, 100 nM) significantly enhanced stimulation-evoked [3H]dopamine release in the presence of the selective dopamine transporter inhibitor 1-[2-[bis-(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride (GBR12909, 100 nM). GBR12909 (100 nM-1 μM), when added alone, increased the evoked [3H]dopamine efflux in a concentration-dependent manner. The stimulatory effect of WIN55,212-2 on the evoked tritium efflux was inhibited by the selective CB1 cannabinoid receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251, 100 nM) and by the GABAA receptor antagonist bicuculline (10 μM). Repeated application of N-methyl-d aspartate (1 mM) under Mg2+-free conditions, which directly acts on dopaminergic terminals, reversibly increased the tritium efflux, but WIN55,212-2 did not affect N-methyl-d aspartate-evoked [3H]dopamine efflux, indicating that WIN55,212-2 has no direct action on dopaminergic nerve terminals. AM251 (100 nM) alone also did not have an effect on electrical stimulation-evoked [3H]dopamine efflux. Likewise, the selective CB2 receptor antagonist 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl)methanone (AM630, 0.3 μM) and the anandamide transport inhibitor (5Z,8Z,11Z,14Z)-N-(4-hydroxy-2-methylphenyl)-5,8,11,14-eicosatetraenamide (VDM11, 10 μM) had no significant effect on electrically evoked [3H]dopamine release. This is the first neurochemical evidence that the activation of CB1 cannabinoid receptors leads to the augmentation of [3H]dopamine efflux via a local GABAA receptor-mediated disinhibitory mechanism in the rat nucleus accumbens.

Original languageEnglish
Pages (from-to)452-457
Number of pages6
JournalNeurochemistry international
Volume54
Issue number7
DOIs
Publication statusPublished - Jun 1 2009

Keywords

  • CB1 receptor
  • Cannabinoid
  • Dopamine
  • GABA
  • Nucleus accumbens
  • Release

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Fingerprint Dive into the research topics of 'Neurochemical evidence that stimulation of CB1 cannabinoid receptors on GABAergic nerve terminals activates the dopaminergic reward system by increasing dopamine release in the rat nucleus accumbens'. Together they form a unique fingerprint.

  • Cite this