Anxiolytic Effects of Buspirone and MTEP in the Porsolt Forced Swim Test
Traditionally, a reduction in floating behavior or immobility in the Porsolt forced swim test is employed as a predictor of anti-depressant efficacy. However, over the past several years, our studies of alcohol withdrawal-induced negative affect consistently indicate the coincidence of increased anx...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2017-06-01
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| Series: | Chronic Stress |
| Online Access: | https://doi.org/10.1177/2470547017712985 |
| _version_ | 1818478866646171648 |
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| author | Kaziya M Lee Michal A Coelho Kimberly R Sern MacKayla A Class Mark D Bocz Karen K Szumlinski |
| author_facet | Kaziya M Lee Michal A Coelho Kimberly R Sern MacKayla A Class Mark D Bocz Karen K Szumlinski |
| author_sort | Kaziya M Lee |
| collection | DOAJ |
| description | Traditionally, a reduction in floating behavior or immobility in the Porsolt forced swim test is employed as a predictor of anti-depressant efficacy. However, over the past several years, our studies of alcohol withdrawal-induced negative affect consistently indicate the coincidence of increased anxiety-related behaviors on various behavioral tests with reduced immobility in the forced swim test. Further, this behavioral profile correlates with increased mGlu5 protein expression within limbic brain regions. As the role for mGlu5 in anxiety is well established, we hypothesized that the reduced immobility exhibited by alcohol-withdrawn mice when tested in the forced swim test might reflect anxiety, possibly a hyper-reactivity to the acute swim stressor. Herein, we evaluated whether or not the decreased forced swim test immobility during alcohol withdrawal responds to systemic treatment with a behaviorally effective dose of the prototypical anxiolytic, buspirone (5 mg/kg). We also determined the functional relevance of the withdrawal-induced increase in mGlu5 expression for forced swim test behavior by comparing the effects of buspirone to a behaviorally effective dose of the mGlu5 negative allosteric modulator MTEP (3 mg/kg). Adult male C57BL/6J mice were subjected to a 14-day, multi-bottle, binge-drinking protocol that elicits hyper-anxiety and increases glutamate-related protein expression during early withdrawal. Control animals received only water. At 24-h withdrawal, animals from each drinking condition were subdivided into groups and treated with an intraperitoneal injection of buspirone, MTEP, or vehicle, 30 min prior to the forced swim test. Drug effects on general locomotor activity were also assessed. As we reported previously, alcohol-withdrawn animals exhibited significantly reduced immobility in the forced swim test compared to water controls. Both buspirone and MTEP significantly increased immobility in alcohol-withdrawn animals, with a modest increase also seen in water controls. No significant group differences were observed for locomotor activity, indicating that neither anxiolytic was sedating. These results provide predictive validity for increased swimming/reduced immobility in the forced swim test as a model of anxiety and provide novel evidence in favor of mGlu5 inhibition as an effective therapeutic strategy for treating hyper-anxiety during alcohol withdrawal. |
| first_indexed | 2024-12-10T09:53:31Z |
| format | Article |
| id | doaj.art-e9fd6384f6c54f6186d6b4e86953aa67 |
| institution | Directory Open Access Journal |
| issn | 2470-5470 |
| language | English |
| last_indexed | 2024-12-10T09:53:31Z |
| publishDate | 2017-06-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Chronic Stress |
| spelling | doaj.art-e9fd6384f6c54f6186d6b4e86953aa672022-12-22T01:53:35ZengSAGE PublishingChronic Stress2470-54702017-06-01110.1177/2470547017712985Anxiolytic Effects of Buspirone and MTEP in the Porsolt Forced Swim TestKaziya M Lee0Michal A Coelho1Kimberly R Sern2MacKayla A Class3Mark D Bocz4Karen K Szumlinski5Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, USADepartment of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, USADepartment of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, USADepartment of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, USADepartment of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, USADepartment of Molecular, Cellular and Developmental Biology, Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA, USATraditionally, a reduction in floating behavior or immobility in the Porsolt forced swim test is employed as a predictor of anti-depressant efficacy. However, over the past several years, our studies of alcohol withdrawal-induced negative affect consistently indicate the coincidence of increased anxiety-related behaviors on various behavioral tests with reduced immobility in the forced swim test. Further, this behavioral profile correlates with increased mGlu5 protein expression within limbic brain regions. As the role for mGlu5 in anxiety is well established, we hypothesized that the reduced immobility exhibited by alcohol-withdrawn mice when tested in the forced swim test might reflect anxiety, possibly a hyper-reactivity to the acute swim stressor. Herein, we evaluated whether or not the decreased forced swim test immobility during alcohol withdrawal responds to systemic treatment with a behaviorally effective dose of the prototypical anxiolytic, buspirone (5 mg/kg). We also determined the functional relevance of the withdrawal-induced increase in mGlu5 expression for forced swim test behavior by comparing the effects of buspirone to a behaviorally effective dose of the mGlu5 negative allosteric modulator MTEP (3 mg/kg). Adult male C57BL/6J mice were subjected to a 14-day, multi-bottle, binge-drinking protocol that elicits hyper-anxiety and increases glutamate-related protein expression during early withdrawal. Control animals received only water. At 24-h withdrawal, animals from each drinking condition were subdivided into groups and treated with an intraperitoneal injection of buspirone, MTEP, or vehicle, 30 min prior to the forced swim test. Drug effects on general locomotor activity were also assessed. As we reported previously, alcohol-withdrawn animals exhibited significantly reduced immobility in the forced swim test compared to water controls. Both buspirone and MTEP significantly increased immobility in alcohol-withdrawn animals, with a modest increase also seen in water controls. No significant group differences were observed for locomotor activity, indicating that neither anxiolytic was sedating. These results provide predictive validity for increased swimming/reduced immobility in the forced swim test as a model of anxiety and provide novel evidence in favor of mGlu5 inhibition as an effective therapeutic strategy for treating hyper-anxiety during alcohol withdrawal.https://doi.org/10.1177/2470547017712985 |
| spellingShingle | Kaziya M Lee Michal A Coelho Kimberly R Sern MacKayla A Class Mark D Bocz Karen K Szumlinski Anxiolytic Effects of Buspirone and MTEP in the Porsolt Forced Swim Test Chronic Stress |
| title | Anxiolytic Effects of Buspirone and MTEP in the Porsolt Forced Swim
Test |
| title_full | Anxiolytic Effects of Buspirone and MTEP in the Porsolt Forced Swim
Test |
| title_fullStr | Anxiolytic Effects of Buspirone and MTEP in the Porsolt Forced Swim
Test |
| title_full_unstemmed | Anxiolytic Effects of Buspirone and MTEP in the Porsolt Forced Swim
Test |
| title_short | Anxiolytic Effects of Buspirone and MTEP in the Porsolt Forced Swim
Test |
| title_sort | anxiolytic effects of buspirone and mtep in the porsolt forced swim test |
| url | https://doi.org/10.1177/2470547017712985 |
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