Exogenous ketone supplements reduce anxiety-related behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk rats
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 exogenou...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2016-12-01
|
| Series: | Frontiers in Molecular Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnmol.2016.00137/full |
| _version_ | 1818583304092254208 |
|---|---|
| author | Csilla Ari Zsolt Kovacs Gabor Juhasz Cem Murdun Craig Robert Goldhagen Andrew Paul Koutnik Angela Marie Poff Shannon L Kesl Dominic Paul D'Agostino |
| author_facet | Csilla Ari Zsolt Kovacs Gabor Juhasz Cem Murdun Craig Robert Goldhagen Andrew Paul Koutnik Angela Marie Poff Shannon L Kesl Dominic Paul D'Agostino |
| author_sort | Csilla Ari |
| collection | DOAJ |
| description | 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 travelled 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. |
| first_indexed | 2024-12-16T08:03:09Z |
| format | Article |
| id | doaj.art-aaa9ab3e1e66466b9b8ddc97c884841a |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-16T08:03:09Z |
| publishDate | 2016-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-aaa9ab3e1e66466b9b8ddc97c884841a2022-12-21T22:38:34ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992016-12-01910.3389/fnmol.2016.00137231152Exogenous ketone supplements reduce anxiety-related behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk ratsCsilla Ari0Zsolt Kovacs1Gabor Juhasz2Cem Murdun3Craig Robert Goldhagen4Andrew Paul Koutnik5Angela Marie Poff6Shannon L Kesl7Dominic Paul D'Agostino8University of South FloridaUniversity of West HungaryEotvos Lorand UniversityUniversity of South FloridaUniversity of South FloridaUniversity of South FloridaUniversity of South FloridaUniversity of South FloridaUniversity of South FloridaNutritional 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 travelled 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.http://journal.frontiersin.org/Journal/10.3389/fnmol.2016.00137/fullAnxietyKetogenic DietKetonesAnimal Modelselevated plus mazeexogenous |
| spellingShingle | Csilla Ari Zsolt Kovacs Gabor Juhasz Cem Murdun Craig Robert Goldhagen Andrew Paul Koutnik Angela Marie Poff Shannon L Kesl Dominic Paul D'Agostino Exogenous ketone supplements reduce anxiety-related behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk rats Frontiers in Molecular Neuroscience Anxiety Ketogenic Diet Ketones Animal Models elevated plus maze exogenous |
| title | Exogenous ketone supplements reduce anxiety-related behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk rats |
| title_full | Exogenous ketone supplements reduce anxiety-related behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk rats |
| title_fullStr | Exogenous ketone supplements reduce anxiety-related behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk rats |
| title_full_unstemmed | Exogenous ketone supplements reduce anxiety-related behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk rats |
| title_short | Exogenous ketone supplements reduce anxiety-related behavior in Sprague-Dawley and Wistar Albino Glaxo/Rijswijk rats |
| title_sort | exogenous ketone supplements reduce anxiety related behavior in sprague dawley and wistar albino glaxo rijswijk rats |
| topic | Anxiety Ketogenic Diet Ketones Animal Models elevated plus maze exogenous |
| url | http://journal.frontiersin.org/Journal/10.3389/fnmol.2016.00137/full |
| work_keys_str_mv | AT csillaari exogenousketonesupplementsreduceanxietyrelatedbehaviorinspraguedawleyandwistaralbinoglaxorijswijkrats AT zsoltkovacs exogenousketonesupplementsreduceanxietyrelatedbehaviorinspraguedawleyandwistaralbinoglaxorijswijkrats AT gaborjuhasz exogenousketonesupplementsreduceanxietyrelatedbehaviorinspraguedawleyandwistaralbinoglaxorijswijkrats AT cemmurdun exogenousketonesupplementsreduceanxietyrelatedbehaviorinspraguedawleyandwistaralbinoglaxorijswijkrats AT craigrobertgoldhagen exogenousketonesupplementsreduceanxietyrelatedbehaviorinspraguedawleyandwistaralbinoglaxorijswijkrats AT andrewpaulkoutnik exogenousketonesupplementsreduceanxietyrelatedbehaviorinspraguedawleyandwistaralbinoglaxorijswijkrats AT angelamariepoff exogenousketonesupplementsreduceanxietyrelatedbehaviorinspraguedawleyandwistaralbinoglaxorijswijkrats AT shannonlkesl exogenousketonesupplementsreduceanxietyrelatedbehaviorinspraguedawleyandwistaralbinoglaxorijswijkrats AT dominicpauldagostino exogenousketonesupplementsreduceanxietyrelatedbehaviorinspraguedawleyandwistaralbinoglaxorijswijkrats |