Lack of interaction of endocannabinoids and 5-HT(3) neurotransmission in associative fear circuits of the amygdala: evidence from electrophysiological and behavioural experiments

Brain Res. 2013 Aug 21:1527:47-56. doi: 10.1016/j.brainres.2013.06.011. Epub 2013 Jun 19.

Abstract

Both the serotonergic and the endocannabinoid system play a major role in mediating fear and anxiety. In the basolateral amygdala (BLA) it has been shown that the cannabinoid receptor 1 (CB1) is highly co-expressed with 5-HT3 receptors on GABAergic interneurons suggesting that 5-HT3 receptor activity modulates CB1-mediated effects on inhibitory synaptic transmission. In the present study, we investigated the possible interactions of CB1 and 5-HT3-mediated neuronal processes in the BLA using electrophysiological and behavioural approaches. Whole-cell patch-clamp recordings were performed in coronal brain slices of mice. Electric stimuli were delivered to the lateral amygdala to evoke GABAA receptor-mediated inhibitory postsynaptic currents (GABAA-eIPSCs) in the BLA. The induction of LTDi, a CB1-mediated depression of inhibitory synaptic transmission, was neither affected by the 5-HT3 antagonists ondansetron (OND; 20 µM) and tropisetron (Trop; 50 nM) nor by the 5-HT3 agonists SR57227A (10 µM). In auditory fear conditioning tests, mice treated with SR57227A (3.0mg/kg i.p.) showed sustained freezing, whereas treatment with Trop (1.0 mg/kg i.p.) decreased the expression of conditioned fear. These effects were overruled by the CB1 antagonist rimonabant (RIM; 3.0 mg/kg), which caused increased freezing with or without co-treatment with Trop. In summary, these experiments do not support a functional interaction between CB1 and 5-HT3 receptors at the level of GABA neurotransmission in the BLA nor in terms of fear regulation.

Keywords: 5-HT3; Amygdala; CB1; Fear conditioning; IPSC; Slice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / metabolism*
  • Animals
  • Conditioning, Classical
  • Electric Stimulation
  • Endocannabinoids / metabolism
  • Fear / physiology*
  • Immunohistochemistry
  • Inhibitory Postsynaptic Potentials / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Neural Inhibition / physiology
  • Neural Pathways / metabolism
  • Patch-Clamp Techniques
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Receptors, Serotonin, 5-HT3 / metabolism*
  • Synaptic Transmission / physiology*
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Endocannabinoids
  • Receptor, Cannabinoid, CB1
  • Receptors, Serotonin, 5-HT3
  • gamma-Aminobutyric Acid