title: Anxiogenic-like effects of chronic cannabidiol administration in rats.
abstract: BACKGROUND
  Several pre-clinical and human-based studies have shown that acutely administered cannabidiol (CBD) can produce anxiolytic-like effects
  
  
  OBJECTIVE
  The present study investigated the effects of chronic administration of CBD on rat behaviour and on the expression of brain proteins.
  
  
  METHODS
  Male Lister-hooded rats (150-200 g, n = 8 per group) received daily injections of CBD (10 mg/kg, i.p.) for 14 days. The rats were subjected to two behavioural tests: locomotor activity and conditioned emotional response (CER). The expression of brain-derived neurotrophic factor (BDNF), its receptor tyrosine kinase B (Trk B), extracellular signal-regulated kinases (ERK1/2) and phospho-ERK1/2 and the transcription factor cyclic AMP response element binding protein activation (CREB) and phospho-CREB were determined in brain regions such as the frontal cortex and hippocampus using Western immunoblotting.
  
  
  RESULTS
  CBD significantly increased the time spent freezing in the CER test with no effect on locomotor activity. CBD significantly reduced BDNF expression in the hippocampus and frontal cortex with no change in the striatum. In addition, CBD significantly reduced TrkB expression in the hippocampus with a strong trend towards reduction in the striatum but had no effect in the frontal cortex. In the hippocampus, CBD had no effect on ERK1/2 or phospho-ERK2, but in the frontal cortex, CBD significantly reduced phospho-ERK1/2 expression without affecting total ERK.
  
  
  CONCLUSIONS
  Chronic administration of CBD produced an anxiogenic-like effect in clear opposition to the acute anxiolytic profile previously reported. In addition, CBD decreased the expression of proteins that have been shown to be enhanced by chronic treatment with antidepressant/anxiolytic drugs.
authors.affiliation: School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, UK. maha.ali@med.menofia.edu.eg
authors.forename: Maha M
authors.initials: MM
authors.lastname: ElBatsh
authors.forename: N
authors.initials: N
authors.lastname: Assareh
authors.forename: C A
authors.initials: CA
authors.lastname: Marsden
authors.forename: D A
authors.initials: DA
authors.lastname: Kendall
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D001522:Behavior, Animal / Q000187:drug effects*; D015153:Blotting, Western; D002185:Cannabidiol / Q000008:administration & dosage / Q000633:toxicity*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats
chemical_list: D002185:Cannabidiol; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
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