PMID- 28479397 OWN - NLM STAT- MEDLINE DCOM- 20170905 LR - 20220408 IS - 1873-7064 (Electronic) IS - 0028-3908 (Print) IS - 0028-3908 (Linking) VI - 121 DP - 2017 Jul 15 TI - Locomotor sensitization to intermittent ketamine administration is associated with nucleus accumbens plasticity in male and female rats. PG - 195-203 LID - S0028-3908(17)30199-5 [pii] LID - 10.1016/j.neuropharm.2017.05.003 [doi] AB - Clinical evidence suggests superior antidepressant response over time with a repeated, intermittent ketamine treatment regimen as compared to a single infusion. However, the club drug ketamine is commonly abused. Therefore, the abuse potential of repeated ketamine injections at low doses needs to be investigated. In this study, we investigated the abuse potential of repeated exposure to either 0, 2.5, or 5 mg/kg ketamine administered once weekly for seven weeks. Locomotor activity and conditioned place preference (CPP) were assayed to evaluate behavioral sensitization to the locomotor activating effects of ketamine and its rewarding properties, respectively. Our results show that while neither males nor females developed CPP, males treated with 5 mg/kg and females treated with either 2.5 or 5 mg/kg ketamine behaviorally sensitized. Furthermore, dendritic spine density was increased in the NAc of both males and females administered 5 mg/kg ketamine, an effect specific to the NAc shell (NAcSh) in males but to both the NAc core (NAcC) and NAcSh in females. Additionally, males administered 5 mg/kg ketamine displayed increased protein expression of DeltafosB, calcium calmodulin kinase II alpha (CaMKIIalpha), and brain-derived neurotrophic factor (BDNF), an effect not observed in females administered either dose of ketamine. However, males and females administered 5 mg/kg ketamine displayed increased protein expression of AMPA receptors (GluA1). Taken together, low-dose ketamine, when administered intermittently, induces behavioral sensitization at a lower dose in females than males, accompanied by an increase in spine density in the NAc and protein expression changes in pathways commonly implicated in addiction. CI - Copyright (c) 2017. Published by Elsevier Ltd. FAU - Strong, C E AU - Strong CE AD - Department of Biomedical Sciences and Program in Neuroscience, Florida State University, Tallahassee, FL, USA. FAU - Schoepfer, K J AU - Schoepfer KJ AD - Department of Biomedical Sciences and Program in Neuroscience, Florida State University, Tallahassee, FL, USA. FAU - Dossat, A M AU - Dossat AM AD - Department of Biomedical Sciences and Program in Neuroscience, Florida State University, Tallahassee, FL, USA. FAU - Saland, S K AU - Saland SK AD - Department of Biomedical Sciences and Program in Neuroscience, Florida State University, Tallahassee, FL, USA. FAU - Wright, K N AU - Wright KN AD - Department of Biomedical Sciences and Program in Neuroscience, Florida State University, Tallahassee, FL, USA. FAU - Kabbaj, M AU - Kabbaj M AD - Department of Biomedical Sciences and Program in Neuroscience, Florida State University, Tallahassee, FL, USA. Electronic address: mohamed.kabbaj@med.fsu.edu. LA - eng GR - R01 MH087583/MH/NIMH NIH HHS/United States GR - R01 MH099085/MH/NIMH NIH HHS/United States GR - R01 MH109450/MH/NIMH NIH HHS/United States PT - Journal Article DEP - 20170504 PL - England TA - Neuropharmacology JT - Neuropharmacology JID - 0236217 RN - 0 (Dopamine Uptake Inhibitors) RN - 690G0D6V8H (Ketamine) RN - I5Y540LHVR (Cocaine) SB - IM MH - Analysis of Variance MH - Animals MH - Cocaine/pharmacology MH - Conditioning, Operant/*drug effects MH - Dopamine Uptake Inhibitors/pharmacology MH - Dose-Response Relationship, Drug MH - Estrous Cycle/drug effects MH - Exploratory Behavior/drug effects MH - Female MH - Ketamine/*pharmacology MH - Locomotion/*drug effects MH - Male MH - Neuronal Plasticity/*drug effects MH - Neurons/drug effects/ultrastructure MH - Nucleus Accumbens/cytology/*drug effects MH - Rats MH - Rats, Sprague-Dawley MH - *Sex Characteristics MH - Silver Staining PMC - PMC5520991 MID - NIHMS878761 OTO - NOTNLM OT - BDNF OT - CPP OT - CaMKIIalpha OT - Drug abuse OT - GluA1 OT - Ketamine OT - Nucleus accumbens OT - Sensitization OT - Sex differences OT - Spine density OT - DeltafosB COIS- The authors declare no conflict of interest. EDAT- 2017/05/10 06:00 MHDA- 2017/09/07 06:00 PMCR- 2018/07/15 CRDT- 2017/05/09 06:00 PHST- 2016/12/21 00:00 [received] PHST- 2017/03/20 00:00 [revised] PHST- 2017/05/03 00:00 [accepted] PHST- 2017/05/10 06:00 [pubmed] PHST- 2017/09/07 06:00 [medline] PHST- 2017/05/09 06:00 [entrez] PHST- 2018/07/15 00:00 [pmc-release] AID - S0028-3908(17)30199-5 [pii] AID - 10.1016/j.neuropharm.2017.05.003 [doi] PST - ppublish SO - Neuropharmacology. 2017 Jul 15;121:195-203. doi: 10.1016/j.neuropharm.2017.05.003. Epub 2017 May 4.