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Cited by 62Cannabis and Cannabinoid ResearchNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

Role of the cyclic-AMP/PKA cascade and of P/Q-type Ca++ channels in endocannabinoid-mediated long-term depression in the nucleus accumbens

Mato, Susana, Lafourcade, Mathieu, Robbe, David, Bakiri, Yamina, Manzoni, Olivier J.·2008·Neuropharmacology
DOI 10.1016/j.neuropharm.2007.04.014
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Abstract

Glutamate transmission between prefrontal cortex (PFC) and accumbens (NAc) plays a crucial role in the establishment and expression of addictive behaviors. At these synapses exogenous cannabinoid receptor 1 (CB1R) agonists reversibly inhibit excitatory transmission, and the sustained release of endogenous cannabinoids (eCB) following prolonged cortical stimulation leads to long-term depression (LTD). Activation of presynaptic K(+) channels mediates the effects of exocannabinoids, but the transduction pathway underlying the protracted phase of eCB-LTD is unknown. Here we report that the maintenance of eCB-LTD does not involve presynaptic K(+) channels: eCB-LTD was not affected by blockade of K(+) channels with 4-AP (100 microM) and BaCl(2) (300 microM) (fEPSP=78.9+/-5.4% of baseline 58-60 min after tetanus, compared to 78.9+/-5.9% in control slices). In contrast, eCB-LTD was blocked by treatment of the slices with the adenylyl cyclase (AC) activator forskolin (10 microM), and with the protein kinase A (PKA) inhibitor KT5720 (1 microM) (fEPSP=108.9+/-5.7% in forskolin and 110.5+/-7.7% in KT5720, compared to 80.6+/-3.9% in control conditions). Additionally, selective blockade of P/Q-type Ca(2+) channels with omega-agatoxin-IVA (200 nM) occluded the expression of eCB-LTD (fEPSP=113.4+/-15.9% compared to 78.6+/-4.4% in control slices), while blockade of N- with omega-conotoxin-GVIA (1 microM) or L-type Ca(2+) channels with nimodipine (1 microM), was without effect (fEPSP was 83.7+/-5.3% and 87+/-8.9% respectively). These data show that protracted inhibition of AC/PKA activity and P/Q-type Ca(2+) channels are necessary for expression of eCB-LTD at NAc synapses.

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Crossref · 10.1016/j.neuropharm.2007.04.014

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  • CB1R negatively regulates N- and P/Q-type voltage-gated calcium channels and positively regulates inwardly rectifying K+ channels, as well as calcineurin, to change the phosphorylation state of effector molecules.

    “In addition, CB1R negatively regulates N- and P/Q-type voltage-gated calcium channels [26] and positively regulates inwardly rectifying K+ channels [26,27], as well as protein serine/threonine phosphatase 2B (calcineurin, PP2B) to change the phosphorylation state of various effector molecules [28,29].”

    From Amygdala FAAH and anandamide: mediating protection and recovery from stress (2013) · cites this paper as [26]

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Authors
Mato, S., Lafourcade, M., Robbe, D., Bakiri, Y., & Manzoni, O. J.
Affiliations
Inserm (FR)
Corresponding author
Manzoni, Olivier J.
ORCID
Venue
Neuropharmacology
Publisher
Elsevier BV
Published
2008-01
Volume
54
Issue
1
Pages
87-94
ISSN
0028-3908 (ISSN-L)
DOI
10.1016/j.neuropharm.2007.04.014
OpenAlex
W2064665634
Cited by
62
References
43
Citations by year
2025: 3 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 6 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 6 · 2016: 3 · 2015: 2 · 2014: 4 · 2013: 5 · 2012: 4
FWCI
1.77
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuropharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Topics
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
nucleus accumbens, P/Q-type calcium channels, adenylate cyclase, presynaptic inhibition, glutamatergic neurotransmission, prefrontal cortex, CB1 receptor, omega-agatoxin IVA, synaptic plasticity, addiction
MeSH terms
Action Potentials, Cyclic AMP, Animals, Calcium, Calcium Channel Blockers, Carbazoles, Chlorides, Electric Stimulation, Enzyme Inhibitors, Colforsin, Indoles, Male, Mice, Inbred C57BL, Nucleus Accumbens, Pyrroles, Signal Transduction, 4-Aminopyridine, Barium Compounds, Patch-Clamp Techniques, Calcium Channels, P-Type, Potassium Channel Blockers, Long-Term Synaptic Depression, Mice, Cannabinoid Receptor Modulators, Endocannabinoids, In Vitro Techniques

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