Intrinsic sensory deprivation induced by neonatal capsaicin treatment induces changes in rat brain and behaviour of possible relevance to schizophrenia

• Published in: British journal of pharmacology 2005-10, Vol.146 (3), p.408-418
• Main Authors: Newson, Penny, Lynch‐Frame, Ann, Roach, Rebecca, Bennett, Sarah, Carr, Vaughan, Chahl, Loris A
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Behavior, Animal - drug effects; Biological and medical sciences; Brain - drug effects; Brain - pathology; Capsaicin; Capsaicin - pharmacology; Cell Count; Female; Male; Medical sciences; neonatal capsaicin; neuronal density; Neurons - cytology; Neurons - drug effects; Organ Size - drug effects; Pharmacology. Drug treatments; rat behaviour; rat brain; Rats; Rats, Wistar; Schizophrenia; Sensory Deprivation; Sex Factors; Tail - drug effects; Tail - growth & development
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0706349

Schizophrenia is considered to be a neurodevelopmental disorder with origins in the prenatal or neonatal period. Brains from subjects with schizophrenia have enlarged ventricles, reduced cortical thickness (CT) and increased neuronal density in the prefrontal cortex compared with those from normal subjects. Subjects with schizophrenia have reduced pain sensitivity and niacin skin flare responses, suggesting that capsaicin‐sensitive primary afferent neurons might be abnormal in schizophrenia. This study tested the hypothesis that intrinsic somatosensory deprivation, induced by neonatal capsaicin treatment, causes changes in the brains of rats similar to those found in schizophrenia. Wistar rats were treated with capsaicin, 50 mg kg−1 subcutaneously, or vehicle (control) at 24–36 h of life. At 5–7 weeks behavioural observations were made, and brains removed, fixed and sectioned. The mean body weight of capsaicin‐treated rats was not significantly different from control, but the mean brain weight of male, but not female, rats, was significantly lower than control. Capsaicin‐treated rats were hyperactive compared with controls. The hyperactivity was abolished by haloperidol. Coronal brain sections of capsaicin‐treated rats had smaller cross‐sectional areas, reduced CT, larger ventricles and aqueduct, smaller hippocampal area and reduced corpus callosum thickness, than brain sections from control rats. Neuronal density was increased in several cortical areas and the caudate putamen, but not in the visual cortex. It is concluded that neonatal capsaicin treatment of rats produces brain changes that are similar to those found in brains of subjects with schizophrenia. British Journal of Pharmacology (2005) 146, 408–418. doi:10.1038/sj.bjp.0706349