Impaired Ethanol-Induced Sensitization and Decreased Cannabinoid Receptor-1 in a Model of Posttraumatic Stress DisorderReportar como inadecuado




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Background and Purpose

Impaired striatal neuroplasticity may underlie increased alcoholism documented in those with posttraumatic stress disorder PTSD. Cannabinoid receptor-1 CB1 is sensitive to the effects of ethanol EtOH and traumatic stress, and is a critical regulator of striatal plasticity. To investigate CB1 involvement in the PTSD-alcohol interaction, this study measured the effects of traumatic stress using a model of PTSD, mouse single-prolonged stress mSPS, on EtOH-induced locomotor sensitization and striatal CB1 levels.

Methods

Mice were exposed to mSPS, which includes: 2-h restraint, 10-min group forced swim, 15-min exposure to rat bedding odor, and diethyl ether exposure until unconsciousness or control conditions. Seven days following mSPS exposure, the locomotor sensitizing effects of EtOH were assessed. CB1, post-synaptic density-95 PSD95, and dopamine-2 receptor D2 protein levels were then quantified in the dorsal striatum using standard immunoblotting techniques.

Results

Mice exposed to mSPS-EtOH demonstrated impaired EtOH-induced locomotor sensitization compared to Control-EtOH mice, which was accompanied by reduced striatal CB1 levels. EtOH increased striatal PSD95 in control and mSPS-exposed mice. Additionally, mSPS-Saline exposure increased striatal PSD95 and decreased D2 protein expression, with mSPS-EtOH exposure alleviating these changes.

Conclusions

These data indicate that the mSPS model of PTSD blunts the behavioral sensitizing effects of EtOH, a response that suggests impaired striatal neuroplasticity. Additionally, this study demonstrates that mice exposed to mSPS and repeated EtOH exposure decreases CB1 in the striatum, providing a mechanism of interest for understanding the effects of EtOH following severe, multimodal stress exposure.



Autor: Jessica J. Matchynski-Franks, Laura L. Susick, Brandy L. Schneider, Shane A. Perrine, Alana C. Conti

Fuente: http://plos.srce.hr/



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