RT Journal Article
SR Electronic
T1 Distribution of CB1 Cannabinoid Receptors in the Amygdala and their Role in the Control of GABAergic Transmission
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 9506
OP 9518
DO 10.1523/JNEUROSCI.21-23-09506.2001
VO 21
IS 23
A1 István Katona
A1 Ede A. Rancz
A1 László Acsády
A1 Catherine Ledent
A1 Ken Mackie
A1 Norbert Hájos
A1 Tamás F. Freund
YR 2001
UL http://www.jneurosci.org/content/21/23/9506.abstract
AB 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.