title: Neonatal handling prevents the effects of phencyclidine in an animal model of negative symptoms of schizophrenia.
abstract: BACKGROUND
  Environmental factors during the neonatal period have long-lasting effects on the brain. Neonatal handling, an early mild stress, enhances the ability to cope with stress in adult rats. In humans, inappropriate stress responses increase the risk of schizophrenia in genetically predisposed individuals. We studied the effect of neonatal handling on the phencyclidine (PCP)-induced immobility time of rats in the forced swimming test (FST, an animal model of negative symptoms of schizophrenia) and on plasma adrenocorticotropic hormone (ACTH) as a measure of hypothalamic-pituitary-adrenal axis (HPA) reactivity.
  
  
  METHODS
  Pups were removed from their mothers 15 min/21 days after birth. Postnatal day 65: animals were submitted to restraint stress. Postnatal day 75: after PCP treatment (5 mg/kg/5 days) animals were submitted to the FST.
  
  
  RESULTS
  Neonatal handling reduced HPA reactivity to passive stress (restraint) but not to active coping stress (forced swimming). Immobilization time was significantly lower in saline- and PCP-treated, handled animals than in non-handled ones. Handling prevented the ACTH increase induced by PCP that was observed in the non-handled rats after FST.
  
  
  CONCLUSIONS
  First, neonatal handling protects animals from acquiring the schizophrenic-like behavior provoked by sub-chronic PCP treatment, which was associated with a reduced HPA activity. Second, the beneficial properties of handling in stress responses seem to depend on the type of stress.
authors.affiliation: Department of Pharmacology & Psychiatry, Scholl of Medicine, University of Cadiz, Spain. tejedor.real@uca.es
authors.forename: Purificación
authors.initials: P
authors.lastname: Tejedor-Real
authors.forename: Mar
authors.initials: M
authors.lastname: Sahagún
authors.forename: Nicole Faucon
authors.initials: NF
authors.lastname: Biguet
authors.forename: Jacques
authors.initials: J
authors.lastname: Mallet
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D006234:Handling, Psychological; D007118:Immunoassay; D008297:Male; D010622:Phencyclidine; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical / Q000379:methods; D012559:Schizophrenia / Q000097:blood / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D012565:Schizophrenic Psychology; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism; D013550:Swimming / Q000523:psychology
chemical_list: D000324:Adrenocorticotropic Hormone; D010622:Phencyclidine