N-arachidonoyl-dopamine tunes synaptic transmission onto dopaminergic neurons by activating both cannabinoid and vanilloid receptors

Silvia Marinelli, Vincenzo Di Marzo, Fulvio Florenzano, Filomena Fezza, Maria Teresa Viscomi, Mario Van Der Stelt, Giorgio Bernardi, Marco Molinari, Mauro Maccarrone, Nicola B. Mercuri

Research output: Contribution to journalArticle

Abstract

In the present study, we used electrophysiological, biochemical, and confocal microscopy techniques, to investigate the functional role of transient receptor potential vanilloid type 1 (TRPV1) and cannabinoid type 1 receptors (CB1-R) in the substantia nigra pars compacta (SNpc) and their stimulation by the endocannabinoid N-arachidonoyl-dopamine (NADA). Liquid chromatography-mass spectrometry analyses revealed that a NADA-like compound is produced in substantia nigra slices, in conditions of hyperactivity. Moreover, the functional role of both TRPV1 and CB1-R in modulating synaptic transmission in this area was suggested by confocal microscopy data, showing TRPV1 and CB1-R immunoreactivity in punctate structures, probably representing synaptic contacts on cell bodies of the SNpc. In patch-clamp recordings from dopamine (DA) neurons of the SNpc, we found that NADA increases or reduces glutamatergic transmission onto DA neurons by activating TRPV1 and CB1 receptors, respectively, whereas it decreases GABAergic transmission via CB1 stimulation. Facilitation of glutamate release through TRPV1 was blocked in the presence of a selective blocker of the putative endocannabinoid membrane transporter (EMT), indicating that NADA needs to be taken up by cells to interact with this receptor. In line with these data, biochemical results demonstrated that NADA selectively acted at CB1-R when its re-uptake was blocked. Altogether these data demonstrate a significant role exerted by the endocannabinoid/endovanilloid NADA in the regulation of synaptic transmission to DA neurons of the SNpc. Moreover, they highlight a key function of the EMT transporter in promoting the stimulation of TRPV1 or CB1-R, thus favoring facilitation or inhibition of glutamate synaptic release.

Original languageEnglish
Pages (from-to)298-308
Number of pages11
JournalNeuropsychopharmacology
Volume32
Issue number2
DOIs
Publication statusPublished - Feb 2007

Fingerprint

TRPV Cation Channels
Cannabinoid Receptors
Dopaminergic Neurons
Synaptic Transmission
Dopamine
Endocannabinoids
Membrane Transport Proteins
Confocal Microscopy
Glutamic Acid
Cannabinoid Receptor CB1
Substantia Nigra
Liquid Chromatography
vanilloid receptor subtype 1
Mass Spectrometry
Pars Compacta

Keywords

  • Cannabinoid receptors
  • Confocal microscopy
  • Endocannabinoid transporter
  • NADA
  • Patch-clamp recordings
  • TRPV1

ASJC Scopus subject areas

  • Pharmacology

Cite this

N-arachidonoyl-dopamine tunes synaptic transmission onto dopaminergic neurons by activating both cannabinoid and vanilloid receptors. / Marinelli, Silvia; Di Marzo, Vincenzo; Florenzano, Fulvio; Fezza, Filomena; Viscomi, Maria Teresa; Van Der Stelt, Mario; Bernardi, Giorgio; Molinari, Marco; Maccarrone, Mauro; Mercuri, Nicola B.

In: Neuropsychopharmacology, Vol. 32, No. 2, 02.2007, p. 298-308.

Research output: Contribution to journalArticle

Marinelli, Silvia ; Di Marzo, Vincenzo ; Florenzano, Fulvio ; Fezza, Filomena ; Viscomi, Maria Teresa ; Van Der Stelt, Mario ; Bernardi, Giorgio ; Molinari, Marco ; Maccarrone, Mauro ; Mercuri, Nicola B. / N-arachidonoyl-dopamine tunes synaptic transmission onto dopaminergic neurons by activating both cannabinoid and vanilloid receptors. In: Neuropsychopharmacology. 2007 ; Vol. 32, No. 2. pp. 298-308.
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AU - Marinelli, Silvia

AU - Di Marzo, Vincenzo

AU - Florenzano, Fulvio

AU - Fezza, Filomena

AU - Viscomi, Maria Teresa

AU - Van Der Stelt, Mario

AU - Bernardi, Giorgio

AU - Molinari, Marco

AU - Maccarrone, Mauro

AU - Mercuri, Nicola B.

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