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Novel cannabinoid-sensitive receptor mediates inhibition of glutamatergic synaptic transmission in the hippocampus.

Abstract

Psychoactive effects of cannabinoids are thought to be mediated, at least in part, by suppression of both glutamate and GABA release via CB1 cannabinoid receptor. Two types of cannabinoid receptor (CB1 and CB2) have been cloned so far. The CB1 receptors are abundantly expressed in the nervous system, whereas CB2 receptors are limited to lymphoid organs (Matsuda et al., 1990; Munro et al., 1993). Immunocytochemical and electrophysiological studies revealed that in the hippocampus CB1 receptors are expressed on axon terminals of GABAergic inhibitory interneurons (Tsou et al., 1999; Katona et al., 1999) and activation of these receptors decreases GABA release (Hájos et al., 2000). Other physiological studies pointed out the involvement of CB1 receptors in the modulation of hippocampal glutamatergic synaptic transmission and long-term potentiation (Stella et al., 1997; Misner and Sullivan, 1999), but anatomical studies could not confirm the existence of CB1 receptors on glutamatergic terminals. Here we examined cannabinoid actions on both glutamatergic and GABAergic synaptic transmission in the hippocampus of wild type (CB1+/+) and CB1 receptor knockout mice (CB1-/-). The synthetic cannabinoid agonist WIN55,212-2 reduced the amplitudes of excitatory postsynaptic currents in both wild type and CB1-/- mice, while inhibitory postsynaptic currents were decreased only in wild type mice, but not in CB1-/- animals. Our findings are consistent with a CB1 cannabinoid receptor-dependent modulation of GABAergic postsynaptic currents, but a novel cannabinoid-sensitive receptor must be responsible for the inhibition of glutamatergic neurotransmission.

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  • Authors+Show Affiliations

    ,

    Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest H-1450, Hungary.

    ,

    Source

    Neuroscience 106:1 2001 pg 1-4

    MeSH

    Analgesics
    Animals
    Benzoxazines
    Cannabinoids
    Electric Stimulation
    Excitatory Amino Acid Antagonists
    Excitatory Postsynaptic Potentials
    GABA Antagonists
    Glutamic Acid
    Hippocampus
    Interneurons
    Mice
    Mice, Knockout
    Morpholines
    Naphthalenes
    Neural Inhibition
    Piperidines
    Pyramidal Cells
    Pyrazoles
    Receptors, Cannabinoid
    Receptors, Drug
    Receptors, GABA
    Receptors, Glutamate
    Rimonabant
    Synapses
    Synaptic Transmission
    gamma-Aminobutyric Acid

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    11564411

    Citation

    Hájos, N, et al. "Novel Cannabinoid-sensitive Receptor Mediates Inhibition of Glutamatergic Synaptic Transmission in the Hippocampus." Neuroscience, vol. 106, no. 1, 2001, pp. 1-4.
    Hájos N, Ledent C, Freund TF. Novel cannabinoid-sensitive receptor mediates inhibition of glutamatergic synaptic transmission in the hippocampus. Neuroscience. 2001;106(1):1-4.
    Hájos, N., Ledent, C., & Freund, T. F. (2001). Novel cannabinoid-sensitive receptor mediates inhibition of glutamatergic synaptic transmission in the hippocampus. Neuroscience, 106(1), pp. 1-4.
    Hájos N, Ledent C, Freund TF. Novel Cannabinoid-sensitive Receptor Mediates Inhibition of Glutamatergic Synaptic Transmission in the Hippocampus. Neuroscience. 2001;106(1):1-4. PubMed PMID: 11564411.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Novel cannabinoid-sensitive receptor mediates inhibition of glutamatergic synaptic transmission in the hippocampus. AU - Hájos,N, AU - Ledent,C, AU - Freund,T F, PY - 2001/9/21/pubmed PY - 2002/1/5/medline PY - 2001/9/21/entrez SP - 1 EP - 4 JF - Neuroscience JO - Neuroscience VL - 106 IS - 1 N2 - Psychoactive effects of cannabinoids are thought to be mediated, at least in part, by suppression of both glutamate and GABA release via CB1 cannabinoid receptor. Two types of cannabinoid receptor (CB1 and CB2) have been cloned so far. The CB1 receptors are abundantly expressed in the nervous system, whereas CB2 receptors are limited to lymphoid organs (Matsuda et al., 1990; Munro et al., 1993). Immunocytochemical and electrophysiological studies revealed that in the hippocampus CB1 receptors are expressed on axon terminals of GABAergic inhibitory interneurons (Tsou et al., 1999; Katona et al., 1999) and activation of these receptors decreases GABA release (Hájos et al., 2000). Other physiological studies pointed out the involvement of CB1 receptors in the modulation of hippocampal glutamatergic synaptic transmission and long-term potentiation (Stella et al., 1997; Misner and Sullivan, 1999), but anatomical studies could not confirm the existence of CB1 receptors on glutamatergic terminals. Here we examined cannabinoid actions on both glutamatergic and GABAergic synaptic transmission in the hippocampus of wild type (CB1+/+) and CB1 receptor knockout mice (CB1-/-). The synthetic cannabinoid agonist WIN55,212-2 reduced the amplitudes of excitatory postsynaptic currents in both wild type and CB1-/- mice, while inhibitory postsynaptic currents were decreased only in wild type mice, but not in CB1-/- animals. Our findings are consistent with a CB1 cannabinoid receptor-dependent modulation of GABAergic postsynaptic currents, but a novel cannabinoid-sensitive receptor must be responsible for the inhibition of glutamatergic neurotransmission. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/11564411/Novel_cannabinoid_sensitive_receptor_mediates_inhibition_of_glutamatergic_synaptic_transmission_in_the_hippocampus_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(01)00287-1 DB - PRIME DP - Unbound Medicine ER -