The infralimbic cortex and mGlu5 mediate the effects of chronic intermittent ethanol exposure on fear learning and memory
| Autor: | C E Smiley, Justin T. Gass, N Otero, R J Newsom, T Valvano, Justin T. McGonigal |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Microinjections Receptor Metabotropic Glutamate 5 Infralimbic cortex Alcohol abuse CDPPB Alcohol use disorder Article 03 medical and health sciences 0302 clinical medicine Memory mental disorders Animals Learning Medicine Fear conditioning Rats Wistar Prefrontal cortex Cerebral Cortex Pharmacology Ethanol business.industry Classical conditioning Fear Extinction (psychology) medicine.disease Rats 030227 psychiatry medicine.anatomical_structure Benzamides Pyrazoles Female business Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Psychopharmacology (Berl) |
| ISSN: | 1432-2072 0033-3158 |
| Popis: | RATIONALE AND OBJECTIVES: Alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) often occur comorbidly. While the incidence of these disorders is increasing, there is little investigation into the interacting neural mechanisms between these disorders. These studies aim to identify cognitive deficits that occur as a consequence of fear and ethanol exposure, implement a novel pharmaceutical intervention, and determine relevant underlying neurocircuitry. Additionally, due to clinical sex differences in PTSD prevalence and alcohol abuse, these studies examine the nature of this relationship in rodent models. METHODS: Animals were exposed to a model of PTSD+AUD using auditory fear conditioning followed by chronic intermittent ethanol exposure (CIE). Then, rats received extinction training consisting of multiple conditioned stimulus presentations in absence of the shock. Extinction recall and context induced freezing were measured in subsequent tests. CDPPB, a metabotropic glutamate receptor 5 (mGlu5) positive allosteric modulator, was used to treat these deficits, and region-specific effects were determined using microinjections. RESULTS: These studies determined that CIE exposure led to deficits in fear extinction learning and heightened context induced freezing while sex-differences emerged in fear conditioning and extinction cue recall tests. Further, using CDPPB, these studies found that enhancement of infralimbic (IfL) mGlu5 activity was able to recover CIE induced deficits in both males and females. CONCLUSIONS: These studies show that CIE induces deficits in fear-related behaviors and that enhancement of IfL glutamatergic activity can facilitate learning during extinction. Additionally, we identify novel pharmacological targets for the treatment of individuals who suffer from PTSD and AUD. |
| Databáze: | OpenAIRE |
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