The CB1 cannabinoid receptor mediates glutamatergic synaptic suppression in the hippocampus.

  • Takahashi K
  • Castillo P
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Abstract

Cannabinoids have profound effects on synaptic function and behavior. Of the two cloned cannabinoid receptors, cannabinoid receptor 1 (CB1) is widely distributed in the CNS and accounts for most of the neurological effects of cannabinoids, while cannabinoid receptor 2 (CB2) expression in the CNS is very limited. The presence of additional receptors [i.e. cannabinoid receptor 3 (CB3)] is suggested by growing evidence of cannabinoid effects that are not mediated by CB1 or CB2. The most direct functional evidence for a CB3 comes from a study in hippocampus where deletion of CB1 was shown to have no effect on cannabinoid-mediated suppression of the excitatory synapse between Schaffer collateral/commissural fibers and CA1 pyramidal cells [Novel cannabinoid-sensitive receptor mediates inhibition of glutamatergic synaptic transmission in the hippocampus. Neuroscience 106:1-4]. In contrast, we report here that in extracellular field recordings, the cannabinoid agonist WIN 55,212-2 (5 microM) had no effect on Schaffer collateral/commissural fiber-CA1 pyramidal cell (Sch-CA1) synaptic transmission in slices from two independently made cannabinoid receptor 1-/- lines [Zimmer et al 1999 and Ledent et al 1999] while strongly suppressing Sch-CA1 synaptic transmission in CB1+/+ mice of the background strains. Also, we observed robust cannabinoid-mediated suppression of the Sch-CA1 synapse in pure C57BL/6 mice, contradicting a recent report that cannabinoid suppression of this synapse is absent in this strain [Hoffman AF, Macgill AM, Smith D, Oz M, Lupica CR (2005) Species and strain differences in the expression of a novel glutamate-modulating cannabinoid receptor in the rodent hippocampus. Eur J Neurosci 22:2387-2391]. Our results strongly suggest that cannabinoid-induced suppression of the Sch-CA1 synapse is mediated by CB1. Non-canonical cannabinoid receptors do not seem to play a major role in inhibiting transmitter release at this synapse.

Author-supplied keywords

  • Animals
  • Benzoxazines
  • CB1
  • CB1: drug effects
  • CB1: metabolism
  • Calcium Channel Blockers
  • Calcium Channel Blockers: pharmacology
  • Cannabinoid
  • Excitatory Postsynaptic Potentials
  • Excitatory Postsynaptic Potentials: drug effects
  • Excitatory Postsynaptic Potentials: physiology
  • Female
  • Glutamine
  • Glutamine: metabolism
  • Hippocampus
  • Hippocampus: drug effects
  • Hippocampus: metabolism
  • Inbred C57BL
  • Knockout
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Morpholines
  • Morpholines: pharmacology
  • Naphthalenes
  • Naphthalenes: pharmacology
  • Organ Culture Techniques
  • Patch-Clamp Techniques
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB1: drug effects
  • Receptor, Cannabinoid, CB1: metabolism
  • Synaptic Transmission
  • Synaptic Transmission: drug effects
  • Synaptic Transmission: physiology

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Authors

  • K a Takahashi

  • Pablo E Castillo

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