Distinct cannabinoid sensitive receptors regulate hippocampal excitation and inhibition

Norbert Hájos, Tamás F. Freund

Research output: Contribution to journalArticle

110 Citations (Scopus)


One of the well-known effects of cannabinoids is the impairment of cognitive processes, including short-term memory formation, by altering hippocampal and neocortical functions reflected in network activity. Acting on presynaptically located G protein-coupled receptors in the hippocampus, cannabinoids modulate the release of neurotransmitter molecules. CB1 cannabinoid receptors, so far the only cloned cannabinoid receptor type in the CNS, are selectively expressed on the axon terminals of a subset of GABAergic inhibitory interneurons containing the neuropeptide cholecystokinin. Activation of CB1 receptors reduces GABA release from presynaptic terminals, thereby increasing the excitability of principal cells. Novel, non-CB1 cannabinoid sensitive receptors are present on the hippocampal excitatory axon terminals, which suppress glutamate release. These cannabinoid receptors have distinct pharmacological features compared to CB1, i.e. WIN 55,212-2 is an order of magnitude less potent in reducing glutamatergic transmission than in inhibiting GABAergic postsynaptic currents, and the novel receptor binds vanilloid receptor ligands. Thus, at least two different cannabinoid sensitive presynaptic receptors regulate network activity in the hippocampus, CB1 via the GABAergic interneurons, and a new receptor via a direct action on pyramidal cell axon terminals.

Original languageEnglish
Pages (from-to)73-82
Number of pages10
JournalChemistry and Physics of Lipids
Issue number1-2
Publication statusPublished - Dec 31 2002



  • CB1 receptor
  • GABA
  • Glutamate
  • Hippocampus
  • Knockout
  • Vanilloid

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Cell Biology

Cite this