Activation of the Cannabinoid Receptor Type 1 Decreases Glutamatergic and GABAergic Synaptic Transmission in the Lateral Amygdala of the Mouse (original) (raw)

  1. Shahnaz Christina Azad1,2,4,
  2. Matthias Eder1,
  3. Giovanni Marsicano3,
  4. Beat Lutz3,
  5. Walter Zieglgänsberger1, and
  6. Gerhard Rammes1
  7. 1Max-Planck-Institute of Psychiatry, Clinical Neuropharmacology, Kraepelinstraße 2-10, 80804 Munich, Germany;2Clinic for Anaesthesiology, Pain Treatment Unit, Ludwig-Maximilians-University, Klinikum Grosshadern, Marchioninistraße, 15, 81377 Munich, Germany;3Max-Planck-Institute of Psychiatry, Molecular Genetics of Behaviour, Kraepelinstraße 2-10, 80804 Munich, Germany

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 GABAA 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 Gi/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 Ca2+ 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.

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