LABORATORY OF TRANSLATIONAL PSYCHIATRY

Background Information

Opioid Addiction

Addiction is defined by American Psychiatric Association in the Diagnosistic and Statistic Manual 5 (DSM-5) as chronic disease of brain reward, motivational, executive and cognitive-related circuitry leading to this illness. It is defined by a problematic pattern of drug use leading to clinically significant impairment or distress, as manifested: Drug is often taken in larger amounts or over a longer period than was intended. There is a persistent desire or unsuccessful efforts to cut down or control drug use. A great deal of time is spent in activities necessary to obtain drug, use drug, or recover from its effects. Craving, or a strong desire or urge to use drug. Recurrent drug use resulting in a failure to fulfill major role obligations at work, school, or home. Recurrent drug use in situations in which it is physically hazardous. Drug use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by drug. Tolerance, as defined by markedly increased amounts of drug to achieve intoxication or desired effect and/or markedly diminished effect with continued use of the same amount of drug. There is a Withdrawal, as manifested by either of characteristic aversive withdrawal syndrome in which the drug is taken to relieve withdrawal symptoms. Our group studies animal models of opioid addiction to understand it neurobiological pathophsiology and to define new and effect approaches for this deadly condition. 

Opioids are addictive substance that produce pain relief and pleasure. While some opioids are legally prescribed to help manage severe pain, some users spiral to abusing their prescription, and seeking opioids beyond their prescribed time. The percentage abuse of prescription opiates is greater than heroin or cocaine abuse. Opioid addiction is a chronic disease with great morbidity and mortality can lead to death by overdose.

Post-Traumatic Stress Disorder (PTSD)

Post-traumatic stress disorder (PTSD) as described by American Psychiatric Association is a psychiatric disorder that occurs in people who have witnessed a traumatic event. There are four types of PTSD symptoms (although varies per person): reliving the event, avoiding reminders of the event, negative changes in beliefs and feelings, and hyperarousal. These symptoms can last from months to years. The exact neurobiology of PTSD is not fully understood, but it is well documented that prefrontal cortex, amygdala, hippocampus, and anterior cingulate cortex are involved. We study animal models of PTSD in order to better understand this condition and to define more effective treatments for this disabling disorder.

Traumatic Brain Injury (TBI)

TBI can result blunt force trauma to the head where the severity leads to altered or loss of consciousness. Depending on the severity of injury, TBI can range from mild (loss of conscious is brief of few seconds to minutes) to moderate (loss of consciousness last minutes to hours) to severe (skull gets crushed or seriously fractured). Mild severity TBI is most common version suffered by Veterans, therefore it is what we focus on. Symptoms of mild TBI include but not limited to: headaches, sensitivity to sound & light, sleep disturbances, impaired concentration & memory, increase in anxiety and depression. Complete recovery of mild TBI takes days to weeks, but symptoms can persist for months and years

Impact on Veterans

At Veteran Affairs Healthcare System, we focus our research to help support Veterans with TBI and PTSD. Unfortunately, the current Iraqi & Afghanistani wars with the advanced explosives and intensive combat in war zones, have lead to almost quarter of the Veteran population suffering TBI, and 40-50% demonstrated PTSD symptoms. Often, the injury leading to TBI comes with traumatic experience causing PTSD.  In fact, 44% of TBI inflicted U.S Army soldiers returning from Iraq had met the criteria for PTSD.

In military and VA settings, soldiers and Veterans face acute or chronic pain that is managed by opiate narcotics. Unfortunately, due the addictive properties of opioids, many Veterans are misuse prescribed opioids, consistent with an Opioid Use Disorder. A study showing over 500,000 veterans who met the criteria for chronic opioid treatment, only 7.5% discontinued opioid use after year. We are examining mechanisms underlying the comorbidity of TBI and potential novel and more effective treatments for both.

TBI & PTSD
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Using Lateral Fluid Percussion for TBI and Fear Conditioning for PTSD on mouse model to see the full spectrum of the comorbid effects: from behavior to neuronal plasticity

PTSD & Opioid Addiction
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With the rise of opioid epidemic, it is imperative to see how the PTSD population are more vulnerable to opioids. We use Fear Conditioning with Opioid Conditioned Place Preference on mouse model to represent the comorbid human condition.

Morphine CPP increases NAc core spine density, not NAc shell

CB57/6BJ mice undergo conditioned place preference (CPP) paradigm to morphine (10 mg/kg) for nine days. After final preference test, mice were Golgi stained to trace neurons for structural plasticity changes in the nucleus accumbens (NAc) in both core and shell. The structural plasticity measures were total dentitric length, number of dendrites, and spine density. Mice exposed to morphine CPP had higher dendritic length and number in NAc compare to both saline and morphine homecage controls (Figure 2A & 2B). There were no significant difference in NAc shell (Figure 2C & 2D). Spine density was also shown to increase in NAc core for morphine CPP compared to saline and morphine homecage controls.

*p<0.05