title: Social isolation stress reduces hippocampal long-term potentiation: effect of animal strain and involvement of glucocorticoid receptors.
abstract: BACKGROUND
  Depressive patients show cognitive impairments that are strongly associated with cortisol levels and hippocampus functioning that interact via unknown mechanisms. In addition, a relation between depression and hippocampal synaptic plasticity was described.
  
  
  METHODS
  In the first experiment, strain-dependent effects of 72-h social isolation on long-term potentiation (LTP) in the CA1 area of the in vitro hippocampus, was determined. Extracellular field excitatory postsynaptic potentials were recorded and a brief high-frequency stimulation (100 Hz, 1s) was applied and recording resumed after the high frequency stimulation (HFS) for 30 min to determine the effect of HFS. In the second experiment we investigated the effect of 72 h of corticosterone treatment and the involvement of glucocorticoid receptors (GRs) in the effect of 72 h of social isolation on LTP in the CA1 area of hippocampus, in vitro.
  
  
  RESULTS
  Genetic background has a major effect on the level of hippocampal LTP impairment in mice following social isolation. Data showed that the potentiation levels in socially housed (SH) A/J mice were significantly higher than the SH C57BL/6J mice (224.88 ± 16.65, 131.56 ± 6.25% of the baseline values, t(9)=2.648, p=0.026). However, both strains showed depressed induction of potentiation when reared in an isolated environment for 72 h, and no significant difference was recorded between the two (112.88 ± 16.65%, and 117.91 ± 3.23% of the baseline values, respectively, t(10)=0.618, p=0.551). Social isolation increased corticosterone levels significantly and chronic corticosterone infusion in SH phenocopied the LTP impairments observed in socially isolated mice. Infusion of the GR antagonist RU38486 rescued the LTP-impairments following social isolation.
  
  
  CONCLUSIONS
  These findings support the notion that increased levels of stress hormone act via the GR on hippocampal functioning and that, in this way, the cognitive deficits in mood disorders may be restored.
authors.affiliation: Rudolf Magnus Institute of Neurosciences, Department of Neuroscience and Pharmacology, UMC Utrecht, Utrecht, The Netherlands; Arabian Gulf University, College of Medicine and Medical Sciences, Department of Physiology, Manama, Bahrain. Electronic address: amerha@agu.edu.bh.
authors.forename: A
authors.initials: A
authors.lastname: Kamal
authors.affiliation: Rudolf Magnus Institute of Neurosciences, Department of Neuroscience and Pharmacology, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: G M J
authors.initials: GM
authors.lastname: Ramakers
authors.affiliation: Rudolf Magnus Institute of Neurosciences, Department of Neuroscience and Pharmacology, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: B
authors.initials: B
authors.lastname: Altinbilek
authors.affiliation: Rudolf Magnus Institute of Neurosciences, Department of Neuroscience and Pharmacology, UMC Utrecht, Utrecht, The Netherlands.
authors.forename: M J H
authors.initials: MJ
authors.lastname: Kas
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001703:Biophysics; D003345:Corticosterone / Q000494:pharmacology; D004333:Drug Administration Routes; D004558:Electric Stimulation; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D006727:Hormone Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015735:Mifepristone / Q000494:pharmacology; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D012934:Social Isolation; D013315:Stress, Psychological / Q000473:pathology*
chemical_list: D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003345:Corticosterone
keywords: GR; HFS; LTD; LTP; MWM; Morris water maze; N-methyl-d-aspartate; NMDA; SH; SI; aCSF; activity-dependent synaptic plasticity; artificial cerebrospinal fluid; cognitive deficits; depression; fEPSP; field excitatory post synaptic potential; glucocorticoid receptor; high frequency stimulation; long-term depression; long-term potentiation; socially housed; socially isolated