title: CB1 cannabinoid receptor activation rescues amyloid β-induced alterations in behaviour and intrinsic electrophysiological properties of rat hippocampal CA1 pyramidal neurones.
abstract: BACKGROUND
  Amyloid beta (Aβ) is believed to be responsible for the synaptic failure that occurs in Alzheimer's disease (AD), but there is little known about the functional impact of Aβ on intrinsic neuronal properties. Here, the cellular effect of Aβ-induced neurotoxicity on the electrophysiological properties of CA1 pyramidal neurons and the mechanism(s) of neuroprotection by CB1 cannabinoid receptor activation was explored.
  
  
  METHODS
  A combination of behavioural, molecular and electrophysiological approaches was used.
  
  
  RESULTS
  Bilateral injections of the Aβ peptide fragment (1-42) into the prefrontal cortex caused a significant impairment in the retention and recall capability in the passive avoidance tasks and significantly increased the level of active caspase-3 in the hippocampus. Whole-cell patch clamp recordings revealed a significant reduction in the intrinsic action potential (AP) frequency and an increase in the discharge irregularity in the absence of synaptic inputs in Aβ treated group. Aβ treatment induced also significant changes in both the spontaneous and evoked neuronal responses. However, co-treatment with ACEA, a CB1 receptor agonist, preserved almost the normal intrinsic electrophysiological properties of pyramidal cells.
  
  
  CONCLUSIONS
  In vivo Aβ treatment altered significantly the intrinsic electrophysiological properties of CA1 pyramidal neurons and the activation of CB1 cannabinoid receptors exerted a strong neuroprotective action against Aβ toxicity.
authors.affiliation: Neuroscience Research Centre and Dept. of Physiology, Medical School, Shahid Beheshti University of Medical Sciences, Evin, Tehran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Haghani
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shabani
authors.forename: Mohammad
authors.initials: M
authors.lastname: Javan
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Motamedi
authors.forename: Mahyar
authors.initials: M
authors.lastname: Janahmadi
mesh_terms: D000200:Action Potentials; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D001362:Avoidance Learning; D001522:Behavior, Animal / Q000187:drug effects*; D048588:Benzoxazines / Q000494:pharmacology; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D055724:Electrophysiological Phenomena; D004789:Enzyme Activation; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000008:administration & dosage / Q000009:adverse effects*; D010880:Piperidines / Q000494:pharmacology; D017966:Pyramidal Cells / Q000378:metabolism / Q000503:physiopathology*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D048588:Benzoxazines; D009025:Morpholines; D009281:Naphthalenes; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C075222:amyloid beta-protein (1-42); C103505:AM 251; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C505410:Casp3 protein, rat; D053148:Caspase 3; D002118:Calcium