Substance use disorder (SUD) is a frequent comorbidity following traumatic brain injury (TBI), even in patients without a previous history of drug use. However, the extent to which the neurological effects of TBI contribute to the development of SUD is unknown. The long-term goal is to understand how brain injury alters neurological and psychiatric function. The objective of the proposed research is to elucidate the relationship between mild TBI (mTBI), addictive phenotypes, and mesocorticolimbic function. The central hypothesis is that mTBI results in elevated risk for drug addiction and changes in mesocorticolimbic circuitry. This hypothesis is supported by correlative data from human studies and by preliminary imaging data using a preclinical mTBI model. The rationale for the proposed research is that understanding the neurological consequences of mTBI will aid in the development of therapeutic strategies for mTBI patients. To isolate neurological effects, we propose a rodent model to enable investigation of the effects of mTBI in drug nave organisms with similar environmental histories. Our hypothesis is supported by epidemiological and preliminary data and will be tested in two specific aims: 1) Identify the impact of mTBI on drug self-administration, seeking, and relapse; and 2) Determine the effects of mTBI and cocaine on brain networks implicated in drug seeking.
In Aim 1, cocaine self-administration and drug seeking will be measured in rats following mild TBI induced by blast forces.
In Aim 2, structural and functional imaging studies will be performed before and after mTBI and cocaine self-administration. The approach is innovative because it will contribute translational imaging and behavioral data from a controlled and reproducible preclinical model to a field of study that has been dominated by human imaging and correlative studies. The project is significant because it will initiate a course of research that will reveal mechanisms of TBI sequelae and how these sequelae can influence drug intake and drug seeking behaviors. This work is expected to contribute to a body of basic research that will aid in the development of treatments for co-morbid psychological and psychiatric disorders following TBI.
This project is relevant to public health because will provide critical information on the neurological and behavioral consequences of mild traumatic brain injury (mTBI). The proposed research is relevant to NIDA's mission because it is directed toward studying adaptations in addictive behaviors and addiction-related brain circuitry following mTBI.
|Nelson, Lindsay D; Furger, Robyn E; Ranson, Jana et al. (2018) Acute Clinical Predictors of Symptom Recovery in Emergency Department Patients with Uncomplicated Mild Traumatic Brain Injury or Non-Traumatic Brain Injuries. J Neurotrauma 35:249-259|
|Nawarawong, Natalie N; Slaker, Megan; Muelbl, Matt et al. (2018) Repeated blast model of mild traumatic brain injury alters oxycodone self-administration and drug seeking. Eur J Neurosci :|
|Muelbl, Matthew J; Slaker, Megan L; Shah, Alok S et al. (2018) Effects of Mild Blast Traumatic Brain Injury on Cognitive- and Addiction-Related Behaviors. Sci Rep 8:9941|
|Stemper, Brian D; Shah, Alok S; Budde, Matthew D et al. (2016) Behavioral Outcomes Differ between Rotational Acceleration and Blast Mechanisms of Mild Traumatic Brain Injury. Front Neurol 7:31|
|Stemper, Brian D; Shah, Alok S; Chiariello, Rachel et al. (2016) Prediction of Post-Concussive Behavioral Changes in a Rodent Model Based on Head Rotational Acceleration Characteristics. Ann Biomed Eng 44:3252-3265|
|Olsen, Christopher M; Liu, Qing-Song (2016) Phosphodiesterase 4 inhibitors and drugs of abuse: current knowledge and therapeutic opportunities. Front Biol (Beijing) 11:376-386|
|Lim, Yi Wei; Meyer, Nathan P; Shah, Alok S et al. (2015) Voluntary Alcohol Intake following Blast Exposure in a Rat Model of Mild Traumatic Brain Injury. PLoS One 10:e0125130|
|Stemper, Brian D; Shah, Alok S; Pintar, Frank A et al. (2015) Head rotational acceleration characteristics influence behavioral and diffusion tensor imaging outcomes following concussion. Ann Biomed Eng 43:1071-88|