title: Activation of the cannabinoid receptor type 1 decreases glutamatergic and GABAergic synaptic transmission in the lateral amygdala of the mouse.
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.
authors.affiliation: Max-Planck-Institute of Psychiatry, Clinical Neuropharmacology, Kraepelinstrasse 2-10, 80804 Munich, Germany. azad@mpipsykl.mpg.de
authors.forename: Shahnaz Christina
authors.initials: SC
authors.lastname: Azad
authors.forename: Matthias
authors.initials: M
authors.lastname: Eder
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marsicano
authors.forename: Beat
authors.initials: B
authors.lastname: Lutz
authors.forename: Walter
authors.initials: W
authors.lastname: Zieglgänsberger
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rammes
mesh_terms: D000679:Amygdala / Q000502:physiology*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D048588:Benzoxazines; D015220:Calcium Channels / Q000502:physiology; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials; D018698:Glutamic Acid / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009433:Neural Inhibition / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology; D018091:Receptors, AMPA / Q000502:physiology; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D000700:Analgesics; D048588:Benzoxazines; D015220:Calcium Channels; D009025:Morpholines; D009281:Naphthalenes; D015221:Potassium Channels; D018091:Receptors, AMPA; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D011963:Receptors, GABA-A; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone