Dexamethasone Attenuates the Enhanced Rewarding Effects of Cocaine Following Experimental Traumatic Brain Injury

نویسندگان

  • Steven F. Merkel
  • Allison M. Andrews
  • Evan M. Lutton
  • Roshanak Razmpour
  • Lee Anne Cannella
  • Servio H. Ramirez
چکیده

Clinical studies have identified traumatic brain injury (TBI) as a risk factor for the development of cocaine dependence. This claim is supported by our recent pre-clinical studies showing enhancement of the rewarding effects of cocaine in mice sustaining moderate controlled cortical impact (CCI) injury during adolescence. Here, we test the efficacy of dexamethasone, an anti-inflammatory corticosteroid, to attenuate augmentation of the behavioral response to cocaine observed in CCI-TBI animals using the conditioned place preference (CPP) assay. These studies were performed in order to determine whether pro-inflammatory activity in the nucleus accumbens (NAc), a key brain nucleus in the reward pathway, mediates enhanced cocaine induced CPP in adolescent animals sustaining moderate CCI-TBI. Our data reveal robust glial activation in the NAc following CCI-TBI and a significant increase in the cocaine induced CPP of untreated CCI-TBI mice. Furthermore, our results show that dexamethasone treatment following CCI-TBI can attenuate the cocaine place preference of injured animals without producing aversion in the CPP assay. Our studies also found that dexamethasone treatment significantly reduced the expression of select immune response genes including CCL2 and ICAM-1, returning their expression to control levels, which prompted an investigation of peripheral blood monocytes in dexamethasone-treated animals. Experimental findings showed that no craniectomy/dexamethasone mice had a significant increase, while CCI-TBI/dexamethasone animals had a significant decrease in the percentage of circulating non-classical patrolling monocytes. These results suggest that a portion of these monocytes may migrate to the brain in response to CCI-TBI, potentially sparing the development of chronic neuroinflammation in regions associated with the reward circuitry such as the NAc. Overall, our findings indicate that anti-inflammatory agents, such as dexamethasone, may be effective in normalizing the rewarding effects of cocaine following CCI-TBI.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Effects of sex steroid hormones on neuromedin S and neuromedin U2 receptor expression following experimental traumatic brain injury

Objective(s): Neuroprotective effects of female gonadal steroids are mediated through several pathways involving multiple peptides and receptors after traumatic brain injury (TBI). Two of these peptides are including the regulatory peptides neuromedin U (NMU) and neuromedin S (NMS), and their common receptor neuromedin U2 receptor (NMUR2). This study investigates the effects of physiological do...

متن کامل

O13: Human Neural Stem/Progenitor Cells Derived from Epileptic Human Brain in A Self-Assembling Peptide Nanoscaffold Attenuates Neuroinlammation in Traumatic Brain Injury in Rats

Traumatic brain injury (TBI) is a disruption in the brain functions following a head trauma. Cell therapy may provide a promising treatment for TBI. Human neural stem cells cultured in self-assembling peptide scaffolds have been proposed as a potential novel method for cell replacement treatment after TBI. In the present study, we accessed the effects of human neural stem/progenitor cells (hNS/...

متن کامل

The Effects of Estrogen Receptors' Antagonist on Brain Edema, Intracranial Pressure and Neurological Outcomes after Traumatic Brain Injury in Rat

Background: In previous studies, the neuroprotective effect of 17&beta-estradiol in diffuse traumatic brain injury has been shown. This study used ICI 182,780, a non-selective estrogen receptor antagonist, to test the hypothesis that the neuroprotective effect of 17&beta-estradiol in traumatic brain injury is mediated by the estrogen receptors. Methods: The ovariectomized rats were divided into...

متن کامل

Neuroprotective Effects of Allicin on Neurological Scores, Blood Brain Barrier Permeability and Brain Edema Following Severe Traumatic Brain Injury in Male Rats: A Behavioral, Biochemical and Histological Study

 Background and purpose: Allicin has a wide range of pharmacological functions, all of which can be demonstrated in anti-inflammatory, antioxidant, antifungal and anti-tumor activities. In this research, we investigated the neuroprotective role of allicin in the process of diffuse traumatic brain injury and its effect on interleukin levels and histological changes in rats. Materials and method...

متن کامل

P80: The Effects of Progesterone Receptors\' Antagonist RU-486 on BrainEdema, Intracranial Pressure and Neurological Outcomes after Traumatic Brain Injury

In previous studies, the neuroprotective effect of progestrone in diffuse traumatic brain injury has been shown. This study used mifepristone (RU-486), a potent progesterone receptor antagonist, to evaluatethe hypothesis that the neuroprotective effect of progesterone in traumatic brain injury is mediated by the progesterone receptors. The ovariectomized rats were divided into 6 groups. Brain i...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 26  شماره 

صفحات  -

تاریخ انتشار 2016