Cannabinoids modulate neuronal firing in the rat basolateral amygdala: evidence for CB1- and non-CB1-mediated actions

Cannabinoids modulate neuronal firing in the rat basolateral amygdala: evidence for CB1- and... Recent evidence indicates that the basolateral amygdala (BLA) may be involved in behavioural effects induced by cannabinoids. High levels of CB1 cannabinoid receptors have been shown in this region, where they modulate excitatory and inhibitory synaptic transmission. However, the neurophysiological effects of these opposing synaptic actions have not been investigated in vivo. To this purpose, single-unit extracellular recordings were performed in urethane anaesthetized rats in order to determine whether exogenously applied cannabinoids influenced the spontaneous or evoked electrical activity of neurons in the BLA. The effects of cannabinoids were found to be dependent on the characteristics of the neurons examined and on the properties of the agents used. We tested and compared two structurally different synthetic cannabinoid receptor agonists, the highly potent HU-210 (0.125–1.0 mg/kg, i.v.) and WIN55212-2 (WIN, 0.125–1.0 mg/kg, i.v.). With a CB1 cannabinoid receptor-dependent mechanism, HU-210 potently inhibited the firing rate of BLA interneurons whereas WIN modulated the discharge rate in a biphasic manner. By contrast, BLA projection neurons, antidromically identified from the shell of the nucleus accumbens, were significantly inhibited by WIN at all doses tested, while HU-210 administration led to less consistent effects, since only 1.0 mg/kg inhibited firing rate in the majority of recorded neurons. Additionally, WIN, but not HU-210, significantly attenuated short-latency spiking activity in BLA projection neurons evoked by electrical stimulation of the medial prefrontal cortex. In these neurons, WIN-induced effects were antagonised by the non-selective cannabinoid receptor antagonist SR141716A and by the vanilloid receptor antagonist capsazepine, but not by the selective CB1 antagonist AM-251. Taken together, our findings indicate that the overall excitability of efferent neurons in the BLA is strongly reduced by WIN in a non-CB1-dependent manner. In this effect, the contribution of a novel cannabinoid-vanilloid-sensitive putative non-CB1 receptors, the existence of which was postulated in recent reports, might play a role. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neuropharmacology Elsevier

Cannabinoids modulate neuronal firing in the rat basolateral amygdala: evidence for CB1- and non-CB1-mediated actions

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Publisher
Elsevier
Copyright
Copyright © 2003 Elsevier Ltd
ISSN
0028-3908
eISSN
1873-7064
DOI
10.1016/j.neuropharm.2003.08.003
Publisher site
See Article on Publisher Site

Abstract

Recent evidence indicates that the basolateral amygdala (BLA) may be involved in behavioural effects induced by cannabinoids. High levels of CB1 cannabinoid receptors have been shown in this region, where they modulate excitatory and inhibitory synaptic transmission. However, the neurophysiological effects of these opposing synaptic actions have not been investigated in vivo. To this purpose, single-unit extracellular recordings were performed in urethane anaesthetized rats in order to determine whether exogenously applied cannabinoids influenced the spontaneous or evoked electrical activity of neurons in the BLA. The effects of cannabinoids were found to be dependent on the characteristics of the neurons examined and on the properties of the agents used. We tested and compared two structurally different synthetic cannabinoid receptor agonists, the highly potent HU-210 (0.125–1.0 mg/kg, i.v.) and WIN55212-2 (WIN, 0.125–1.0 mg/kg, i.v.). With a CB1 cannabinoid receptor-dependent mechanism, HU-210 potently inhibited the firing rate of BLA interneurons whereas WIN modulated the discharge rate in a biphasic manner. By contrast, BLA projection neurons, antidromically identified from the shell of the nucleus accumbens, were significantly inhibited by WIN at all doses tested, while HU-210 administration led to less consistent effects, since only 1.0 mg/kg inhibited firing rate in the majority of recorded neurons. Additionally, WIN, but not HU-210, significantly attenuated short-latency spiking activity in BLA projection neurons evoked by electrical stimulation of the medial prefrontal cortex. In these neurons, WIN-induced effects were antagonised by the non-selective cannabinoid receptor antagonist SR141716A and by the vanilloid receptor antagonist capsazepine, but not by the selective CB1 antagonist AM-251. Taken together, our findings indicate that the overall excitability of efferent neurons in the BLA is strongly reduced by WIN in a non-CB1-dependent manner. In this effect, the contribution of a novel cannabinoid-vanilloid-sensitive putative non-CB1 receptors, the existence of which was postulated in recent reports, might play a role.

Journal

NeuropharmacologyElsevier

Published: Jan 1, 2004

References

  • The amygdala and reward
    Baxter, M.G.; Murray, E.A.
  • Pharmacological separation of cannabinoid sensitive receptors on hippocampal excitatory and inhibitory fibers
    Hajos, N.; Freund, T.F.
  • Expression of the cannabinoid receptor CB1 in distinct neuronal subpopulations in the adult mouse forebrain
    Marsicano, G.; Lutz, B.
  • Novel, not adenylyl cyclase-coupled cannabinoid binding site in cerebellum of mice
    Monory, K.; Tzavara, E.T.; Lexime, J.; Ledent, C.; Parmentier, M.; Borsodi, A.; Hanoune, J.
  • Cannabinoids inhibit excitatory inputs to neurons in the shell of the nucleus accumbens: an in vivo electrophysiological study
    Pistis, M.; Muntoni, A.L.; Pillolla, G.; Gessa, G.L.
  • Excitatory transmission in the basolateral amygdala
    Rainnie, D.G.; Asprodini, E.K.; Shinnick-Gallagher, P.
  • Inhibitory transmission in the basolateral amygdala
    Rainnie, D.G.; Asprodini, E.K.; Shinnick-Gallagher, P.
  • Excitatory amino acid receptors in the basolateral amygdala regulate anxiety responses in the social interaction test
    Sajdyk, T.J.; Shekhar, A.
  • Amino acid-mediated regulation of spontaneous synaptic activity patterns in the rat basolateral amygdala
    Smith, B.N.; Dudek, F.E.

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