PreprintCited by 220Cannabis and Cannabinoid ResearchNeuroscience and Neuropharmacology ResearchMemory and Neural Mechanisms

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Activation of the Cannabinoid Receptor Type 1 Decreases Glutamatergic and GABAergic Synaptic Transmission in the Lateral Amygdala of the Mouse

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Azad, Shahnaz Christina, Eder, Matthias, Marsicano, Giovanni, Lutz, Beat, Zieglgänsberger, Walter, Rammes, Gerhard·2003·Learning & Memory

DOI 10.1101/lm.53303PMC PMC196665

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Abstract

The endogenous cannabinoid system has been shown recently to play a crucial role in the extinction of aversive memories. As the amygdala is presumably involved in this process, we investigated the effects of the cannabinoid receptor agonist WIN 55,212-2 (WIN-2) on synaptic transmission in the lateral amygdala (LA) of wild-type and cannabinoid receptor type 1 (CB1)-deficient mice. Extracellular field potential recordings and patch-clamp experiments were performed in an in vitro slice preparation. We found that WIN-2 reduces basal synaptic transmission and pharmacologically isolated AMPA receptor- and GABA(A) receptor-mediated postsynaptic currents in wild-type, but not in CB1-deficient mice. These results indicate that, in the LA, cannabinoids modulate both excitatory and inhibitory synaptic transmission via CB1. WIN-2-induced changes of paired-pulse ratio and of spontaneous and miniature postsynaptic currents suggest a presynaptic site of action. Inhibition of G(i/o) proteins and blockade of voltage-dependent and G protein-gated inwardly rectifying K(+) channels inhibited WIN-2 action on basal synaptic transmission. In contrast, modulation of the adenylyl cyclase-protein kinase A pathway, and blockade of presynaptic N- and P/Q- or of postsynaptic L- and R/T-type voltage-gated Ca(2+) channels did not affect WIN-2 effects. Our results indicate that the mechanisms underlying cannabinoid action in the LA partly resemble those observed in the nucleus accumbens and differ from those described for the hippocampus.

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Authors: Azad, S. C., Eder, M., Marsicano, G., Lutz, B., Zieglgänsberger, W., & Rammes, G.
Affiliations: LMU Klinikum (DE)
ORCID: Eder, Matthias
Marsicano, Giovanni
Lutz, Beat
Rammes, Gerhard
Venue: Learning & Memory
Publisher: Cold Spring Harbor Laboratory
Published: 2003-03-01
Volume: 10
Issue: 2
Pages: 116-128
ISSN: 1072-0502 (ISSN-L)
1549-5485
DOI: 10.1101/lm.53303
PMC: PMC196665
OpenAlex: W2134429437
Cited by: 220
References: 51
Citations by year: 2026: 5 · 2025: 2 · 2024: 3 · 2023: 1 · 2022: 7 · 2021: 5 · 2020: 11 · 2019: 6 · 2018: 10 · 2017: 10 · 2016: 10 · 2015: 9 · 2014: 12 · 2013: 9 · 2012: 7
Type: posted content
Language: en
Open access: bronze
doi.org
Locations: Learning & Memory (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Max Planck Institute for Plasma Physics (submittedVersion)
mediaTUM (Technical University of Munich) (submittedVersion)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords: cannabinoid receptor type 1, WIN 55,212-2, lateral amygdala, synaptic transmission, AMPA receptors, GABAA receptor, presynaptic modulation, G protein signaling, inwardly rectifying potassium channels, voltage-gated calcium channels, endocannabinoid system
MeSH terms: Amygdala, Analgesics, Animals, Electrophysiology, gamma-Aminobutyric Acid, Male, Mice, Inbred C57BL, Mice, Transgenic, Morpholines, Naphthalenes, Neural Inhibition, Synaptic Transmission, Receptors, Drug, Receptors, GABA-A, Calcium Channels, Potassium Channels, Receptors, AMPA, Patch-Clamp Techniques, Glutamic Acid, Excitatory Postsynaptic Potentials, Receptors, Cannabinoid, Benzoxazines, Mice

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Activation of the Cannabinoid Receptor Type 1 Decreases Glutamatergic and GABAergic Synaptic Transmission in the Lateral Amygdala of the Mouse

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