Cyclooxygenase-2 inhibition reduces stress-induced affective pathology
Mood and anxiety disorders are the most prevalent psychiatric conditions and are exacerbated by stress. Recent studies have suggested cyclooxygenase-2 (COX-2) inhibition could represent a novel treatment approach or augmentation strategy for affective disorders including anxiety disorders and major...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2016-05-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/14137 |
| _version_ | 1818018642314395648 |
|---|---|
| author | Joyonna Carrie Gamble-George Rita Baldi Lindsay Halladay Adrina Kocharian Nolan Hartley Carolyn Grace Silva Holly Roberts Andre Haymer Lawrence J Marnett Andrew Holmes Sachin Patel |
| author_facet | Joyonna Carrie Gamble-George Rita Baldi Lindsay Halladay Adrina Kocharian Nolan Hartley Carolyn Grace Silva Holly Roberts Andre Haymer Lawrence J Marnett Andrew Holmes Sachin Patel |
| author_sort | Joyonna Carrie Gamble-George |
| collection | DOAJ |
| description | Mood and anxiety disorders are the most prevalent psychiatric conditions and are exacerbated by stress. Recent studies have suggested cyclooxygenase-2 (COX-2) inhibition could represent a novel treatment approach or augmentation strategy for affective disorders including anxiety disorders and major depression. We show that traditional COX-2 inhibitors and a newly developed substrate-selective COX-2 inhibitor (SSCI) reduce a variety of stress-induced behavioral pathologies in mice. We found that these behavioral effects were associated with a dampening of neuronal excitability in the basolateral amygdala (BLA) ex vivo and in vivo, and were mediated by small-conductance calcium-activated potassium (SK) channel and CB1 cannabinoid receptor activation. Taken together, these data provide further support for the potential utility of SSCIs, as well as traditional COX-2 inhibitors, as novel treatment approaches for stress-related psychiatric disorders. |
| first_indexed | 2024-04-14T07:42:15Z |
| format | Article |
| id | doaj.art-868e80d931654ad3bc72774df54cbe0c |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:42:15Z |
| publishDate | 2016-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-868e80d931654ad3bc72774df54cbe0c2022-12-22T02:05:27ZengeLife Sciences Publications LtdeLife2050-084X2016-05-01510.7554/eLife.14137Cyclooxygenase-2 inhibition reduces stress-induced affective pathologyJoyonna Carrie Gamble-George0https://orcid.org/0000-0002-5492-9216Rita Baldi1Lindsay Halladay2Adrina Kocharian3Nolan Hartley4Carolyn Grace Silva5Holly Roberts6Andre Haymer7Lawrence J Marnett8Andrew Holmes9Sachin Patel10https://orcid.org/0000-0001-8052-520XDepartment of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, United States; Vanderbilt Brain Institute, Vanderbilt University, Nashville, United StatesDepartment of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, United StatesLaboratory of Behavioral and Genomic Neuroscience, National Institute on Alcoholism and Alcohol Abuse, Bethesda, United StatesLaboratory of Behavioral and Genomic Neuroscience, National Institute on Alcoholism and Alcohol Abuse, Bethesda, United StatesDepartment of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, United States; Vanderbilt Brain Institute, Vanderbilt University, Nashville, United StatesDepartment of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, United StatesDepartment of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, United StatesDepartment of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, United StatesA.B. Hancock Jr. Memorial Laboratory for Cancer Research, Departments of Biochemistry, Chemistry, and Pharmacology, Vanderbilt Institute of Chemical Biology, Center in Molecular Toxicology, and Vanderbilt-Ingram Cancer Center, Nashville, United StatesLaboratory of Behavioral and Genomic Neuroscience, National Institute on Alcoholism and Alcohol Abuse, Bethesda, United StatesDepartment of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, United States; Vanderbilt Brain Institute, Vanderbilt University, Nashville, United States; Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, United States; Vanderbilt Kennedy Center for Human Development, Vanderbilt University Medical Center, Nashville, United StatesMood and anxiety disorders are the most prevalent psychiatric conditions and are exacerbated by stress. Recent studies have suggested cyclooxygenase-2 (COX-2) inhibition could represent a novel treatment approach or augmentation strategy for affective disorders including anxiety disorders and major depression. We show that traditional COX-2 inhibitors and a newly developed substrate-selective COX-2 inhibitor (SSCI) reduce a variety of stress-induced behavioral pathologies in mice. We found that these behavioral effects were associated with a dampening of neuronal excitability in the basolateral amygdala (BLA) ex vivo and in vivo, and were mediated by small-conductance calcium-activated potassium (SK) channel and CB1 cannabinoid receptor activation. Taken together, these data provide further support for the potential utility of SSCIs, as well as traditional COX-2 inhibitors, as novel treatment approaches for stress-related psychiatric disorders.https://elifesciences.org/articles/14137COX-2anxietycannabinoidPTSDamygdalastress |
| spellingShingle | Joyonna Carrie Gamble-George Rita Baldi Lindsay Halladay Adrina Kocharian Nolan Hartley Carolyn Grace Silva Holly Roberts Andre Haymer Lawrence J Marnett Andrew Holmes Sachin Patel Cyclooxygenase-2 inhibition reduces stress-induced affective pathology eLife COX-2 anxiety cannabinoid PTSD amygdala stress |
| title | Cyclooxygenase-2 inhibition reduces stress-induced affective pathology |
| title_full | Cyclooxygenase-2 inhibition reduces stress-induced affective pathology |
| title_fullStr | Cyclooxygenase-2 inhibition reduces stress-induced affective pathology |
| title_full_unstemmed | Cyclooxygenase-2 inhibition reduces stress-induced affective pathology |
| title_short | Cyclooxygenase-2 inhibition reduces stress-induced affective pathology |
| title_sort | cyclooxygenase 2 inhibition reduces stress induced affective pathology |
| topic | COX-2 anxiety cannabinoid PTSD amygdala stress |
| url | https://elifesciences.org/articles/14137 |
| work_keys_str_mv | AT joyonnacarriegamblegeorge cyclooxygenase2inhibitionreducesstressinducedaffectivepathology AT ritabaldi cyclooxygenase2inhibitionreducesstressinducedaffectivepathology AT lindsayhalladay cyclooxygenase2inhibitionreducesstressinducedaffectivepathology AT adrinakocharian cyclooxygenase2inhibitionreducesstressinducedaffectivepathology AT nolanhartley cyclooxygenase2inhibitionreducesstressinducedaffectivepathology AT carolyngracesilva cyclooxygenase2inhibitionreducesstressinducedaffectivepathology AT hollyroberts cyclooxygenase2inhibitionreducesstressinducedaffectivepathology AT andrehaymer cyclooxygenase2inhibitionreducesstressinducedaffectivepathology AT lawrencejmarnett cyclooxygenase2inhibitionreducesstressinducedaffectivepathology AT andrewholmes cyclooxygenase2inhibitionreducesstressinducedaffectivepathology AT sachinpatel cyclooxygenase2inhibitionreducesstressinducedaffectivepathology |