Cannabinoids inhibit excitatory neurotransmission in the substantia nigra pars reticulata

Szabó, Béla; Wallmichrath, Ilka; Mathonia, P; Pfreundtner, C

doi:10.1016/s0306-4522(00)00036-1

Cited by 118 publications

(70 citation statements)

References 44 publications

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“…This is in agreement with earlier studies reporting a presynaptic modulation of neurotransmission by CB1-R in several brain regions, especially in the ventral midbrain (Szabo et al, 2000;Gerdeman and Lovinger, 2001;Huang et al, 2001Huang et al, , 2002aAzad et al, 2003;Melis et al, 2004).…”

Section: Discussionsupporting

confidence: 94%

N-Arachidonoyl-Dopamine Tunes Synaptic Transmission onto Dopaminergic Neurons by Activating both Cannabinoid and Vanilloid Receptors

Marinelli

Marzo

Florenzano

et al. 2006

Neuropsychopharmacol

149

117

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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.

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Section: Discussionsupporting

confidence: 94%

N-Arachidonoyl-Dopamine Tunes Synaptic Transmission onto Dopaminergic Neurons by Activating both Cannabinoid and Vanilloid Receptors

Marinelli

Marzo

Florenzano

et al. 2006

Neuropsychopharmacol

149

117

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“…CB1-R expressed by MSNs and located in the extrastriatal terminals could also regulate ERK activation by acting at the circuit level. For example, in the substantia nigra pars reticulata, stimulation of CB1-R decreases striatonigral GABAergic transmission (Szabo et al, 2000). If a similar effect exists in striatopallidal terminals of the indirect pathway, stimulation of CB1-R would result in a decreased activity of nigrothalamic neurons and, through multisynaptic circuits (Chevalier and Deniau, 1990), to an increased corticostriatal excitatory transmission.…”

Section: Discussionmentioning

confidence: 99%

Role of Cannabinoid Type 1 Receptors in Locomotor Activity and Striatal Signaling in Response to Psychostimulants

Corbillé¹,

Valjent²,

Marsicano³

et al. 2007

Journal of Neuroscience

113

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A single administration of cocaine or D-amphetamine produces acute hyperlocomotion and long-lasting increased sensitivity to subsequent injections. This locomotor sensitization reveals the powerful ability of psychostimulants to induce brain plasticity and may participate in the alterations that underlie addiction. We investigated the role of cannabinoid receptor type 1 (CB1-R) in the effects of a single injection of psychostimulants. The acute locomotor response to cocaine was normal in mice pretreated with the CB1-R inverse agonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251), whereas no sensitization was observed in response to a second administration a week later. Locomotor responses to cocaine and D-amphetamine were decreased in CB1-R-deficient mice, and sensitization was impaired. To determine how CB1-R controls long-lasting effects of psychostimulants, we studied cocaine-activated signaling pathways. Cocaine-induced cAMP-dependent phosphorylation of glutamate receptor 1 was altered in the striatum of CB1-R mutant mice but not of AM251-treated mice. In contrast, cocaine-induced phosphorylation of extracellular signal-regulated kinase (ERK) was blocked in both CB1-R mutant and antagonist-pretreated mice. Conditional deletion of CB1-R in forebrain principal neurons or GABAergic neurons prevented cocaine-induced ERK activation in dorsal striatum and nucleus accumbens. Our results provide strong evidence for the role of the endocannabinoid system in regulating neuronal circuits critical for long-lasting effects of cocaine, presumably by acting on CB1-R located on terminals of striatal medium spiny neurons.

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“…According to a current model, glutamate released from excitatory terminals activates metabotropic receptors on dendrites Inhibition of glutamatergic neurotransmission by cannabinoid agonists has been documented in a variety of brain structures besides the hippocampus and cerebellum. These include the prefrontal cortex 134 , amygdala 86 , nucleus accumbens 85 , striatum 79 and substantia nigra pars reticulata 135 . Whether such effects reflect the existence of regional DSE-like phenomena is an important question that remains to be addressed.…”

Section: Enduring Inhibitionsmentioning

confidence: 99%

The molecular logic of endocannabinoid signalling

2003

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Cannabinoids inhibit excitatory neurotransmission in the substantia nigra pars reticulata

Cited by 118 publications

References 44 publications

N-Arachidonoyl-Dopamine Tunes Synaptic Transmission onto Dopaminergic Neurons by Activating both Cannabinoid and Vanilloid Receptors

N-Arachidonoyl-Dopamine Tunes Synaptic Transmission onto Dopaminergic Neurons by Activating both Cannabinoid and Vanilloid Receptors

Role of Cannabinoid Type 1 Receptors in Locomotor Activity and Striatal Signaling in Response to Psychostimulants

The molecular logic of endocannabinoid signalling

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