title: Molecular changes in the medial prefrontal cortex and nucleus accumbens are associated with blocking the behavioral sensitization to cocaine.
abstract: Previous studies have demonstrated that cocaine-induced behavioral sensitization is associated with persistent functional and structural alterations in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc); however, the molecular mechanisms underlying these changes have not been elucidated. In this study, the behavioral sensitization to cocaine was established in Sprague Dawley rats and was measured by locomotion and behavioral rating. The brain tissue homogenization was used for measuring the level of brain-derived neurotrophic factor (BDNF), the expression and activity of integrin-linked kinase (ILK), level of protein kinase B (Akt) phosphorylation at serine 473 and threonine 308, and the expression of p75(NTR), TrkA, and TrkB protein. The Results showed that cocaine sensitization was associated with increased BDNF, ILK activity, phospho-Akt Ser(473), p75(NTR), and TrkB protein levels in the mPFC and NAc core. The combination of pergolide and ondansetron normalized not only behavioral sensitization, but also the increases in these molecular markers. Dual immunofluoresence staining showed that ILK expression is co-distributed with p75(NTR) and TrkA expression in both the mPFC and NAc core. Results suggested that the BDNF-TrkA/p75(NTR)-ILK-Akt signaling pathway may be active in cocaine sensitization and associated neural plasticity in the mPFC and NAc core.
authors.affiliation: Medical Psychological institute, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.|Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21221, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Medical Psychological institute, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Xiongzhao
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Cardio-thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China.
authors.forename: Can
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21221, USA.
authors.forename: Xiuwu
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000099200:Scaffold Protein ILK
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D003042:Cocaine; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000099200:Scaffold Protein ILK