Exogenous Ketone supplements reduce anxiety-related behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk rats

Csilla Ari, Z. Kovács, Gabor Juhasz, Cem Murdun, Craig R. Goldhagen, Andrew M. Koutnik, Angela M. Poff, Shannon L. Kesl, Dominic P. D’Agostino

Research output: Article

21 Citations (Scopus)

Abstract

Nutritional ketosis has been proven effective for seizure disorders and other neurological disorders. The focus of this study was to determine the effects of ketone supplementation on anxiety-related behavior in Sprague-Dawley (SPD) and Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats. We tested exogenous ketone supplements added to food and fed chronically for 83 days in SPD rats and administered sub-chronically for 7 days in both rat models by daily intragastric gavage bolus followed by assessment of anxiety measures on elevated plus maze (EPM). The groups included standard diet (SD) or SD + ketone supplementation. Low-dose ketone ester (LKE; 1,3-butanediol-acetoacetate diester, ~10 g/kg/day, LKE), high dose ketone ester (HKE; ~25 g/kg/day, HKE), beta-hydroxybutyrate-mineral salt (βHB-S; ~25 g/kg/day, KS) and βHB-S + medium chain triglyceride (MCT; ~25 g/kg/day, KSMCT) were used as ketone supplementation for chronic administration. To extend our results, exogenous ketone supplements were also tested sub-chronically on SPD rats (KE, KS and KSMCT; 5 g/kg/day) and on WAG/Rij rats (KE, KS and KSMCT; 2.5 g/kg/day). At the end of treatments behavioral data collection was conducted manually by a blinded observer and with a video-tracking system, after which blood βHB and glucose levels were measured. Ketone supplementation reduced anxiety on EPM as measured by less entries to closed arms (sub-chronic KE and KS: SPD rats and KSMCT: WAG/Rij rats), more time spent in open arms (sub-chronic KE: SPD and KSMCT: WAG/Rij rats; chronic KSMCT: SPD rats), more distance traveled in open arms (chronic KS and KSMCT: SPD rats) and by delayed latency to entrance to closed arms (chronic KSMCT: SPD rats), when compared to control. Our data indicates that chronic and sub-chronic ketone supplementation not only elevated blood βHB levels in both animal models, but reduced anxiety-related behavior. We conclude that ketone supplementation may represent a promising anxiolytic strategy through a novel means of inducing nutritional ketosis.

Original languageEnglish
Article number137
JournalFrontiers in Molecular Neuroscience
Volume9
Issue numberDEC2016
DOIs
Publication statusPublished - dec. 6 2016

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Ketones
Anxiety
Sprague Dawley Rats
Ketosis
Esters
Diet
3-Hydroxybutyric Acid
Anti-Anxiety Agents
Nervous System Diseases
Minerals
Blood Glucose
Epilepsy
Triglycerides
Animal Models
Salts
Food

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Exogenous Ketone supplements reduce anxiety-related behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk rats. / Ari, Csilla; Kovács, Z.; Juhasz, Gabor; Murdun, Cem; Goldhagen, Craig R.; Koutnik, Andrew M.; Poff, Angela M.; Kesl, Shannon L.; D’Agostino, Dominic P.

In: Frontiers in Molecular Neuroscience, Vol. 9, No. DEC2016, 137, 06.12.2016.

Research output: Article

Ari, Csilla ; Kovács, Z. ; Juhasz, Gabor ; Murdun, Cem ; Goldhagen, Craig R. ; Koutnik, Andrew M. ; Poff, Angela M. ; Kesl, Shannon L. ; D’Agostino, Dominic P. / Exogenous Ketone supplements reduce anxiety-related behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk rats. In: Frontiers in Molecular Neuroscience. 2016 ; Vol. 9, No. DEC2016.
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AU - Murdun, Cem

AU - Goldhagen, Craig R.

AU - Koutnik, Andrew M.

AU - Poff, Angela M.

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AU - D’Agostino, Dominic P.

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