NDLI: Reinforcing properties of an intermittent, low dose of ketamine in rats: effects of sex and cycle

Content Provider	Springer Nature Link
Author	Wright, Katherine N. Strong, Caroline E. Addonizio, Marjorie N. Brownstein, Naomi C. Kabbaj, Mohamed
Copyright Year	2016
Abstract	Repeated intermittent exposure to ketamine has rapid and long-lasting antidepressant effects, but the abuse potential has only been assessed at high doses. Furthermore, while females are more susceptible to depression and more sensitive to ketamine’s antidepressant-like effects, the abuse potential for ketamine in females is unknown.The objectives of this study are to determine the reinforcing properties of low-dose intermittent ketamine in adult rats of both sexes and determine whether cycling gonadal hormones influence females’ response to ketamine. In male rats, we also aimed to determine whether reinstatement to intermittent ketamine is comparable to intermittent cocaine.Male rats intravenously self-administered cocaine (0.75 mg/kg/infusion) or ketamine (0.1 mg/kg/infusion) once every fourth day, while intact cycling female rats self-administered ketamine only during preidentified stages of their 4-day estrus cycle, when gonadal hormones are either high (proestrus) or low (diestrus). After acquiring self-administration, rats underwent daily extinction training followed by cue-primed and drug-primed reinstatement to assess drug-seeking behavior.Diestrus-trained females fail to maintain ketamine self-administration and did not display reinstatement to ketamine-paired cues. Males and proestrus-trained females reinstated to ketamine-paired cues. Ketamine-primed reinstatement was dependent on simultaneous cue presentation. Male rats reinstated to cocaine priming independent of cue presentation.These findings indicate that females’s responsivity to this dose of ketamine depends on stage of cycle, as only proestrus-trained females and males respond to ketamine’s reinforcing effects under this treatment paradigm.
Starting Page	393
Ending Page	401
Page Count	9
File Format	PDF
ISSN	00333158
Journal	Psychopharmacology
Volume Number	234
Issue Number	3
e-ISSN	14322072
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2016-11-11
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Ketamine Self-administration Females Estrous cycle Intermittent Reinstatement Relapse Neurosciences Pharmacology/Toxicology Psychiatry
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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