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Locomotor sensitization to intermittent ketamine administration is associated with nucleus accumbens plasticity in male and female rats.

Title: Locomotor sensitization to intermittent ketamine administration is associated with nucleus accumbens plasticity in male and female rats.
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Name(s): Strong, C E, author
Schoepfer, K J, author
Dossat, A M, author
Saland, S K, author
Wright, K N, author
Kabbaj, M, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2017-07-15
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: 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 ΔfosB, calcium calmodulin kinase II alpha (CaMKIIα), 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.
Identifier: FSU_pmch_28479397 (IID), 10.1016/j.neuropharm.2017.05.003 (DOI), PMC5520991 (PMCID), 28479397 (RID), 28479397 (EID), S0028-3908(17)30199-5 (PII)
Keywords: BDNF, CPP, CaMKIIα, Drug abuse, GluA1, Ketamine, Nucleus accumbens, Sensitization, Sex differences, Spine density, ΔfosB
Grant Number: R01 MH087583, R01 MH099085
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5520991.
Subject(s): Analysis of Variance
Animals
Cocaine/pharmacology
Conditioning, Operant/drug effects
Dopamine Uptake Inhibitors/pharmacology
Dose-Response Relationship, Drug
Estrous Cycle/drug effects
Exploratory Behavior/drug effects
Female
Ketamine/pharmacology
Locomotion/drug effects
Male
Neuronal Plasticity/drug effects
Neurons/drug effects
Neurons/ultrastructure
Nucleus Accumbens/cytology
Nucleus Accumbens/drug effects
Rats
Rats, Sprague-Dawley
Sex Characteristics
Silver Staining
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_28479397
Owner Institution: FSU
Is Part Of: Neuropharmacology.
1873-7064
Issue: vol. 121

Choose the citation style.
Strong, C. E., Schoepfer, K. J., Dossat, A. M., Saland, S. K., Wright, K. N., & Kabbaj, M. (2017). Locomotor sensitization to intermittent ketamine administration is associated with nucleus accumbens plasticity in male and female rats. Neuropharmacology. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_28479397