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Sex Differences in Effects of Ketamine on Behavior, Spine Density, and Synaptic Proteins in Socially Isolated Rats.

Title: Sex Differences in Effects of Ketamine on Behavior, Spine Density, and Synaptic Proteins in Socially Isolated Rats.
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Name(s): Sarkar, Ambalika, author
Kabbaj, Mohamed, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2016-09-15
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: The mechanistic underpinnings of sex differences in occurrence of depression and efficacy of antidepressant treatments are poorly understood. We examined the effects of isolation stress (IS) and the fast-acting antidepressant ketamine on anhedonia and depression-like behavior, spine density, and synaptic proteins in male and female rats. We used a chronic social IS paradigm to test the effects of ketamine (0, 2.5 mg/kg, and 5 mg/kg) on behavior and levels of synaptic proteins synapsin-1, postsynaptic density protein 95, and glutamate receptor 1 in male rats and female rats in diestrus. Medial prefrontal cortex spine density was also examined in male rats and female rats that received ketamine during either the diestrus or the proestrus phase of their estrous cycle. Male rats showed anhedonia and depression-like behavior after 8 weeks of IS, concomitant with decreases in spine density and levels of synapsin-1, postsynaptic density protein 95, and glutamate receptor 1 in the medial prefrontal cortex; these changes were reversed by a single injection of ketamine (5 mg/kg). After 11 weeks of IS, female rats showed depression-like behavior but no signs of anhedonia. Although both doses of ketamine rescued depression-like behavior in female rats, the decline observed in synaptic proteins and spine density in IS and in diestrus female rats could not be reversed by ketamine. Spine density was higher in female rats during proestrus than in diestrus. Our findings implicate a role for synaptic proteins synapsin-1, postsynaptic density protein 95, and glutamate receptor 1 and medial prefrontal cortex spine density in the antidepressant effects of ketamine in male rats subjected to IS but not in female rats subjected to IS, suggesting dissimilar underlying mechanisms for efficacy of ketamine in the two sexes.
Identifier: FSU_pmch_26957131 (IID), 10.1016/j.biopsych.2015.12.025 (DOI), PMC4940294 (PMCID), 26957131 (RID), 26957131 (EID), S0006-3223(16)00010-X (PII)
Keywords: Anhedonia, Depression, Ketamine, Sex difference, Social isolation, MPFC
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/PMC4940294.
Subject(s): Anhedonia/drug effects
Animals
Behavior, Animal/drug effects
Dendritic Spines/drug effects
Dendritic Spines/pathology
Depression/drug therapy
Depression/psychology
Disks Large Homolog 4 Protein
Estrous Cycle
Female
Intracellular Signaling Peptides and Proteins/metabolism
Ketamine/pharmacology
Male
Membrane Proteins/metabolism
Prefrontal Cortex/drug effects
Prefrontal Cortex/metabolism
Rats
Receptors, Glutamate/metabolism
Sex Characteristics
Social Isolation/psychology
Stress, Psychological/metabolism
Stress, Psychological/psychology
Synapsins/metabolism
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_26957131
Owner Institution: FSU
Is Part Of: Biological psychiatry.
1873-2402
Issue: iss. 6, vol. 80

Choose the citation style.
Sarkar, A., & Kabbaj, M. (2016). Sex Differences in Effects of Ketamine on Behavior, Spine Density, and Synaptic Proteins in Socially Isolated Rats. Biological Psychiatry. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_26957131