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Distribution of CB1 cannabinoid receptors in the amygdala and their role in the control of GABAergic transmission.

Abstract

Cannabinoids are the most popular illicit drugs used for recreational purposes worldwide. However, the neurobiological substrate of their mood-altering capacity has not been elucidated so far. Here we report that CB1 cannabinoid receptors are expressed at high levels in certain amygdala nuclei, especially in the lateral and basal nuclei, but are absent in other nuclei (e.g., in the central nucleus and in the medial nucleus). Expression of the CB1 protein was restricted to a distinct subpopulation of GABAergic interneurons corresponding to large cholecystokinin-positive cells. Detailed electron microscopic investigation revealed that CB1 receptors are located presynaptically on cholecystokinin-positive axon terminals, which establish symmetrical GABAergic synapses with their postsynaptic targets. The physiological consequence of this particular anatomical localization was investigated by whole-cell patch-clamp recordings in principal cells of the lateral and basal nuclei. CB1 receptor agonists WIN 55,212-2 and CP 55,940 reduced the amplitude of GABA(A) receptor-mediated evoked and spontaneous IPSCs, whereas the action potential-independent miniature IPSCs were not significantly affected. In contrast, CB1 receptor agonists were ineffective in changing the amplitude of IPSCs in the rat central nucleus and in the basal nucleus of CB1 knock-out mice. These results suggest that cannabinoids target specific elements in neuronal networks of given amygdala nuclei, where they presynaptically modulate GABAergic synaptic transmission. We propose that these anatomical and physiological features, characteristic of CB1 receptors in several forebrain regions, represent the neuronal substrate for endocannabinoids involved in retrograde synaptic signaling and may explain some of the emotionally relevant behavioral effects of cannabinoid exposure.

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  • Authors+Show Affiliations

    ,

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

    , , , , ,

    Source

    MeSH

    Amygdala
    Analgesics
    Animals
    Benzoxazines
    Cannabinoid Receptor Modulators
    Cannabinoids
    Cholecystokinin
    Cyclohexanols
    Interneurons
    Male
    Membrane Potentials
    Mice
    Mice, Knockout
    Morpholines
    Naphthalenes
    Nerve Net
    Neural Inhibition
    Organ Specificity
    Patch-Clamp Techniques
    Presynaptic Terminals
    Rats
    Rats, Wistar
    Receptors, Cannabinoid
    Receptors, Drug
    Receptors, GABA-A
    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

    11717385

    Citation

    Katona, I, et al. "Distribution of CB1 Cannabinoid Receptors in the Amygdala and Their Role in the Control of GABAergic Transmission." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 21, no. 23, 2001, pp. 9506-18.
    Katona I, Rancz EA, Acsady L, et al. Distribution of CB1 cannabinoid receptors in the amygdala and their role in the control of GABAergic transmission. J Neurosci. 2001;21(23):9506-18.
    Katona, I., Rancz, E. A., Acsady, L., Ledent, C., Mackie, K., Hajos, N., & Freund, T. F. (2001). Distribution of CB1 cannabinoid receptors in the amygdala and their role in the control of GABAergic transmission. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 21(23), pp. 9506-18.
    Katona I, et al. Distribution of CB1 Cannabinoid Receptors in the Amygdala and Their Role in the Control of GABAergic Transmission. J Neurosci. 2001 Dec 1;21(23):9506-18. PubMed PMID: 11717385.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Distribution of CB1 cannabinoid receptors in the amygdala and their role in the control of GABAergic transmission. AU - Katona,I, AU - Rancz,E A, AU - Acsady,L, AU - Ledent,C, AU - Mackie,K, AU - Hajos,N, AU - Freund,T F, PY - 2001/11/22/pubmed PY - 2002/1/12/medline PY - 2001/11/22/entrez SP - 9506 EP - 18 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 21 IS - 23 N2 - Cannabinoids are the most popular illicit drugs used for recreational purposes worldwide. However, the neurobiological substrate of their mood-altering capacity has not been elucidated so far. Here we report that CB1 cannabinoid receptors are expressed at high levels in certain amygdala nuclei, especially in the lateral and basal nuclei, but are absent in other nuclei (e.g., in the central nucleus and in the medial nucleus). Expression of the CB1 protein was restricted to a distinct subpopulation of GABAergic interneurons corresponding to large cholecystokinin-positive cells. Detailed electron microscopic investigation revealed that CB1 receptors are located presynaptically on cholecystokinin-positive axon terminals, which establish symmetrical GABAergic synapses with their postsynaptic targets. The physiological consequence of this particular anatomical localization was investigated by whole-cell patch-clamp recordings in principal cells of the lateral and basal nuclei. CB1 receptor agonists WIN 55,212-2 and CP 55,940 reduced the amplitude of GABA(A) receptor-mediated evoked and spontaneous IPSCs, whereas the action potential-independent miniature IPSCs were not significantly affected. In contrast, CB1 receptor agonists were ineffective in changing the amplitude of IPSCs in the rat central nucleus and in the basal nucleus of CB1 knock-out mice. These results suggest that cannabinoids target specific elements in neuronal networks of given amygdala nuclei, where they presynaptically modulate GABAergic synaptic transmission. We propose that these anatomical and physiological features, characteristic of CB1 receptors in several forebrain regions, represent the neuronal substrate for endocannabinoids involved in retrograde synaptic signaling and may explain some of the emotionally relevant behavioral effects of cannabinoid exposure. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/11717385/Distribution_of_CB1_cannabinoid_receptors_in_the_amygdala_and_their_role_in_the_control_of_GABAergic_transmission_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=11717385 DB - PRIME DP - Unbound Medicine ER -