PMID- 26538265 OWN - NLM STAT- MEDLINE DCOM- 20160923 LR - 20211203 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 5 DP - 2015 Nov 5 TI - Molecular changes in the medial prefrontal cortex and nucleus accumbens are associated with blocking the behavioral sensitization to cocaine. PG - 16172 LID - 10.1038/srep16172 [doi] LID - 16172 AB - 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. FAU - Zhang, Yi AU - Zhang Y AD - Medical Psychological institute, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China. AD - Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21221, USA. FAU - Zhu, Xiongzhao AU - Zhu X AD - Medical Psychological institute, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China. FAU - Huang, Can AU - Huang C AD - Department of Cardio-thoracic Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, P.R. China. FAU - Zhang, Xiuwu AU - Zhang X AD - Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD 21221, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151105 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Brain-Derived Neurotrophic Factor) RN - EC 2.7.1.- (integrin-linked kinase) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - I5Y540LHVR (Cocaine) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cocaine/*pharmacology MH - Male MH - Neuronal Plasticity/drug effects/physiology MH - Nucleus Accumbens/*drug effects/*metabolism/physiology MH - Phosphorylation/drug effects/physiology MH - Prefrontal Cortex/*drug effects/*metabolism/physiology MH - Protein Serine-Threonine Kinases/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - Rats MH - Rats, Sprague-Dawley PMC - PMC4633640 EDAT- 2015/11/06 06:00 MHDA- 2016/09/24 06:00 PMCR- 2015/11/05 CRDT- 2015/11/06 06:00 PHST- 2015/08/03 00:00 [received] PHST- 2015/10/07 00:00 [accepted] PHST- 2015/11/06 06:00 [entrez] PHST- 2015/11/06 06:00 [pubmed] PHST- 2016/09/24 06:00 [medline] PHST- 2015/11/05 00:00 [pmc-release] AID - srep16172 [pii] AID - 10.1038/srep16172 [doi] PST - epublish SO - Sci Rep. 2015 Nov 5;5:16172. doi: 10.1038/srep16172.