Corticosterone as a Potential Confounding Factor in Delineating Mechanisms Underlying Ketamine’s Rapid Antidepressant Actions
Recent research into the rapid antidepressant effect of subanesthetic doses of ketamine have identified a series of relevant protein cascades activated within hours of administration. Prior to, or concurrent with, these activation cascades, ketamine treatment generates dissociative and psychotomimet...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-11-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2020.590221/full |
| _version_ | 1818384417370931200 |
|---|---|
| author | Lauren Wegman-Points Brock Pope Allison Zobel-Mask Lori Winter Eric Wauson Vanja Duric Li-Lian Yuan |
| author_facet | Lauren Wegman-Points Brock Pope Allison Zobel-Mask Lori Winter Eric Wauson Vanja Duric Li-Lian Yuan |
| author_sort | Lauren Wegman-Points |
| collection | DOAJ |
| description | Recent research into the rapid antidepressant effect of subanesthetic doses of ketamine have identified a series of relevant protein cascades activated within hours of administration. Prior to, or concurrent with, these activation cascades, ketamine treatment generates dissociative and psychotomimetic side effects along with an increase in circulating glucocorticoids. In rats, we observed an over 3-fold increase in corticosterone levels in both serum and brain tissue, within an hour of administration of low dose ketamine (10 mg/kg), but not with (2R, 6R)-hydroxynorketamine (HNK) (10 mg/kg), a ketamine metabolite shown to produce antidepressant-like action in rodents without inducing immediate side-effects. Hippocampal tissue from ketamine, but not HNK, injected animals displayed a significant increase in the expression of sgk1, a downstream effector of glucocorticoid receptor signaling. To examine the role conscious sensation of ketamine’s side effects plays in the release of corticosterone, we assessed serum corticosterone levels after ketamine administration while under isoflurane anesthesia. Under anesthesia, ketamine failed to increase circulating corticosterone levels relative to saline controls. Concurrent with its antidepressant effects, ketamine generates a release of glucocorticoids potentially linked to disturbing cognitive side effects and the activation of distinct molecular pathways which should be considered when attempting to delineate the molecular mechanisms of its antidepressant function. |
| first_indexed | 2024-12-14T03:21:56Z |
| format | Article |
| id | doaj.art-414a23b2a8a34bcda3905dabb747bcf2 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-14T03:21:56Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-414a23b2a8a34bcda3905dabb747bcf22022-12-21T23:19:00ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-11-011110.3389/fphar.2020.590221590221Corticosterone as a Potential Confounding Factor in Delineating Mechanisms Underlying Ketamine’s Rapid Antidepressant ActionsLauren Wegman-PointsBrock PopeAllison Zobel-MaskLori WinterEric WausonVanja DuricLi-Lian YuanRecent research into the rapid antidepressant effect of subanesthetic doses of ketamine have identified a series of relevant protein cascades activated within hours of administration. Prior to, or concurrent with, these activation cascades, ketamine treatment generates dissociative and psychotomimetic side effects along with an increase in circulating glucocorticoids. In rats, we observed an over 3-fold increase in corticosterone levels in both serum and brain tissue, within an hour of administration of low dose ketamine (10 mg/kg), but not with (2R, 6R)-hydroxynorketamine (HNK) (10 mg/kg), a ketamine metabolite shown to produce antidepressant-like action in rodents without inducing immediate side-effects. Hippocampal tissue from ketamine, but not HNK, injected animals displayed a significant increase in the expression of sgk1, a downstream effector of glucocorticoid receptor signaling. To examine the role conscious sensation of ketamine’s side effects plays in the release of corticosterone, we assessed serum corticosterone levels after ketamine administration while under isoflurane anesthesia. Under anesthesia, ketamine failed to increase circulating corticosterone levels relative to saline controls. Concurrent with its antidepressant effects, ketamine generates a release of glucocorticoids potentially linked to disturbing cognitive side effects and the activation of distinct molecular pathways which should be considered when attempting to delineate the molecular mechanisms of its antidepressant function.https://www.frontiersin.org/articles/10.3389/fphar.2020.590221/fullketaminehydroxynorketamineglucocorticoidscorticosteronerapid-acting antidepressantstress |
| spellingShingle | Lauren Wegman-Points Brock Pope Allison Zobel-Mask Lori Winter Eric Wauson Vanja Duric Li-Lian Yuan Corticosterone as a Potential Confounding Factor in Delineating Mechanisms Underlying Ketamine’s Rapid Antidepressant Actions Frontiers in Pharmacology ketamine hydroxynorketamine glucocorticoids corticosterone rapid-acting antidepressant stress |
| title | Corticosterone as a Potential Confounding Factor in Delineating Mechanisms Underlying Ketamine’s Rapid Antidepressant Actions |
| title_full | Corticosterone as a Potential Confounding Factor in Delineating Mechanisms Underlying Ketamine’s Rapid Antidepressant Actions |
| title_fullStr | Corticosterone as a Potential Confounding Factor in Delineating Mechanisms Underlying Ketamine’s Rapid Antidepressant Actions |
| title_full_unstemmed | Corticosterone as a Potential Confounding Factor in Delineating Mechanisms Underlying Ketamine’s Rapid Antidepressant Actions |
| title_short | Corticosterone as a Potential Confounding Factor in Delineating Mechanisms Underlying Ketamine’s Rapid Antidepressant Actions |
| title_sort | corticosterone as a potential confounding factor in delineating mechanisms underlying ketamine s rapid antidepressant actions |
| topic | ketamine hydroxynorketamine glucocorticoids corticosterone rapid-acting antidepressant stress |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2020.590221/full |
| work_keys_str_mv | AT laurenwegmanpoints corticosteroneasapotentialconfoundingfactorindelineatingmechanismsunderlyingketaminesrapidantidepressantactions AT brockpope corticosteroneasapotentialconfoundingfactorindelineatingmechanismsunderlyingketaminesrapidantidepressantactions AT allisonzobelmask corticosteroneasapotentialconfoundingfactorindelineatingmechanismsunderlyingketaminesrapidantidepressantactions AT loriwinter corticosteroneasapotentialconfoundingfactorindelineatingmechanismsunderlyingketaminesrapidantidepressantactions AT ericwauson corticosteroneasapotentialconfoundingfactorindelineatingmechanismsunderlyingketaminesrapidantidepressantactions AT vanjaduric corticosteroneasapotentialconfoundingfactorindelineatingmechanismsunderlyingketaminesrapidantidepressantactions AT lilianyuan corticosteroneasapotentialconfoundingfactorindelineatingmechanismsunderlyingketaminesrapidantidepressantactions |