Repeated social defeat stress enhances glutamatergic synaptic plasticity in the VTA and cocaine place conditioning
Enduring memories of sensory cues associated with drug intake drive addiction. It is well known that stressful experiences increase addiction vulnerability. However, it is not clear how repeated stress promotes learning of cue-drug associations, as repeated stress generally impairs learning and memo...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2016-07-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/15448 |
| _version_ | 1811200148034813952 |
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| author | Claire E Stelly Matthew B Pomrenze Jason B Cook Hitoshi Morikawa |
| author_facet | Claire E Stelly Matthew B Pomrenze Jason B Cook Hitoshi Morikawa |
| author_sort | Claire E Stelly |
| collection | DOAJ |
| description | Enduring memories of sensory cues associated with drug intake drive addiction. It is well known that stressful experiences increase addiction vulnerability. However, it is not clear how repeated stress promotes learning of cue-drug associations, as repeated stress generally impairs learning and memory processes unrelated to stressful experiences. Here, we show that repeated social defeat stress in rats causes persistent enhancement of long-term potentiation (LTP) of NMDA receptor-mediated glutamatergic transmission in the ventral tegmental area (VTA). Protein kinase A-dependent increase in the potency of inositol 1,4,5-triphosphate-induced Ca2+ signaling underlies LTP facilitation. Notably, defeated rats display enhanced learning of contextual cues paired with cocaine experience assessed using a conditioned place preference (CPP) paradigm. Enhancement of LTP in the VTA and cocaine CPP in behaving rats both require glucocorticoid receptor activation during defeat episodes. These findings suggest that enhanced glutamatergic plasticity in the VTA may contribute, at least partially, to increased addiction vulnerability following repeated stressful experiences. |
| first_indexed | 2024-04-12T02:00:02Z |
| format | Article |
| id | doaj.art-3372c7abdcd04270b6400d0d63bbe19e |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:00:02Z |
| publishDate | 2016-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-3372c7abdcd04270b6400d0d63bbe19e2022-12-22T03:52:42ZengeLife Sciences Publications LtdeLife2050-084X2016-07-01510.7554/eLife.15448Repeated social defeat stress enhances glutamatergic synaptic plasticity in the VTA and cocaine place conditioningClaire E Stelly0Matthew B Pomrenze1Jason B Cook2Hitoshi Morikawa3https://orcid.org/0000-0002-2948-493XDepartment of Neuroscience, University of Texas, Austin, United States; Waggoner Center for Alcohol and Addiction Research, University of Texas, Austin, United StatesWaggoner Center for Alcohol and Addiction Research, University of Texas, Austin, United States; Division of Pharmacology and Toxicology, University of Texas, Austin, United StatesDepartment of Neuroscience, University of Texas, Austin, United States; Waggoner Center for Alcohol and Addiction Research, University of Texas, Austin, United StatesDepartment of Neuroscience, University of Texas, Austin, United States; Waggoner Center for Alcohol and Addiction Research, University of Texas, Austin, United StatesEnduring memories of sensory cues associated with drug intake drive addiction. It is well known that stressful experiences increase addiction vulnerability. However, it is not clear how repeated stress promotes learning of cue-drug associations, as repeated stress generally impairs learning and memory processes unrelated to stressful experiences. Here, we show that repeated social defeat stress in rats causes persistent enhancement of long-term potentiation (LTP) of NMDA receptor-mediated glutamatergic transmission in the ventral tegmental area (VTA). Protein kinase A-dependent increase in the potency of inositol 1,4,5-triphosphate-induced Ca2+ signaling underlies LTP facilitation. Notably, defeated rats display enhanced learning of contextual cues paired with cocaine experience assessed using a conditioned place preference (CPP) paradigm. Enhancement of LTP in the VTA and cocaine CPP in behaving rats both require glucocorticoid receptor activation during defeat episodes. These findings suggest that enhanced glutamatergic plasticity in the VTA may contribute, at least partially, to increased addiction vulnerability following repeated stressful experiences.https://elifesciences.org/articles/15448addictionsynaptic plasticitydopaminestress |
| spellingShingle | Claire E Stelly Matthew B Pomrenze Jason B Cook Hitoshi Morikawa Repeated social defeat stress enhances glutamatergic synaptic plasticity in the VTA and cocaine place conditioning eLife addiction synaptic plasticity dopamine stress |
| title | Repeated social defeat stress enhances glutamatergic synaptic plasticity in the VTA and cocaine place conditioning |
| title_full | Repeated social defeat stress enhances glutamatergic synaptic plasticity in the VTA and cocaine place conditioning |
| title_fullStr | Repeated social defeat stress enhances glutamatergic synaptic plasticity in the VTA and cocaine place conditioning |
| title_full_unstemmed | Repeated social defeat stress enhances glutamatergic synaptic plasticity in the VTA and cocaine place conditioning |
| title_short | Repeated social defeat stress enhances glutamatergic synaptic plasticity in the VTA and cocaine place conditioning |
| title_sort | repeated social defeat stress enhances glutamatergic synaptic plasticity in the vta and cocaine place conditioning |
| topic | addiction synaptic plasticity dopamine stress |
| url | https://elifesciences.org/articles/15448 |
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