title: Lack of interaction of endocannabinoids and 5-HT(3) neurotransmission in associative fear circuits of the amygdala: evidence from electrophysiological and behavioural experiments.
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.
authors.affiliation: Department of Anaesthesiology, Technische Universität, D-81675 Munich, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Höfelmann
authors.forename: B
authors.initials: B
authors.lastname: di Benedetto
authors.forename: S C
authors.initials: SC
authors.lastname: Azad
authors.forename: V
authors.initials: V
authors.lastname: Micale
authors.forename: C T
authors.initials: CT
authors.lastname: Wotjak
authors.forename: G
authors.initials: G
authors.lastname: Rammes
mesh_terms: D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D003214:Conditioning, Classical; D004558:Electric Stimulation; D063388:Endocannabinoids / Q000378:metabolism; D005239:Fear / Q000502:physiology*; D007150:Immunohistochemistry; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways / Q000378:metabolism; D018408:Patch-Clamp Techniques; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1; D044406:Receptors, Serotonin, 5-HT3; D005680:gamma-Aminobutyric Acid
keywords: 5-HT3; Amygdala; CB1; Fear conditioning; IPSC; Slice