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The Journal of Neuroscience, December 1, 2001, 21(23):9506-9518
Distribution of CB1 Cannabinoid Receptors in the Amygdala and
their Role in the Control of GABAergic Transmission
István
Katona1,
Ede A.
Rancz1,
László
Acsády1,
Catherine
Ledent2,
Ken
Mackie3,
Norbert
Hájos1, and
Tamás F.
Freund1
1 Institute of Experimental Medicine, Hungarian Academy
of Sciences, Budapest, H-1450, Hungary, 2 Institut de
Recherche Interdisciplinaire en Biologie Humaine et Nucléaire,
Université libre de Bruxelles, B-1070 Brussels, Belgium, and
3 Departments of Anesthesiology, and Physiology and
Biophysics, University of Washington, Seattle, Washington 98195
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 GABAA 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.
Key words:
endocannabinoids; interneurons; inhibition; CCK; retrograde signaling; anxiety
Copyright © 2001 Society for Neuroscience 0270-6474/01/21239506-13$05.00/0
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