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Mood-altering drugs have become an unavoidable part of the modern landscape. Whether they come in the form of medically-supervised anti-depressants, or as illegal substances obtained on the street, these drugs affect emotions by altering neurochemical and electrophysiological activities of the brain. Impaired function of the brain reward system is implicated in both depression and addiction, and these two states have documented comorbidity. The neurochemical and electrophysiological changes induced in the brain as a result of these two conditions can be viewed as an expression of brain plasticity, which is the main focus of our studies on depression and addiction. Our goal is to better understand mechanisms by which the brain reward system affects mood and motivation and how this system is altered in states like addiction and depression or their potential therapies. We use animal models for depression and addiction and seek to develop new methods to examine neuronal processes at the root of depressive behavior and drug addiction, thereby finding new treatments for these devastating disorders.
Drug addiction is associated with long lasting neural adaptation in the brain reward system, and pathological usurpation of neural processes that normally serve reward-related learning. In an attempt to affect neural adaptation induced by repeated exposure to abused drugs, we are studying the neurochemical and behavioral effects of repeated intracranial electrical stimulation of reward-related brain sites in animal models and transcranial magnetic stimulation in humans. (MORE DETAILS)
In the world of drug abuse, the recovering addict is in a constant state of conflict, wherein he or she must choose between the rewarding effects of the drug, and the negative consequences of renewed drug use (relapse). Despite dedicated and innovative work using animal models, many studies of relapse seem to fall short of paralleling relapse in humans. Thus, we created a conflict model of cue-induced relapse in rats that approximates the human condition that will allow us to further study the neural processes of drug relapse and its potential prevention. (MORE DETAILS)
In-vivo electrophysiological recording allows us to further examine plasticity-related alterations in the function of the brain reward system that are critically involved in drug addiction or depressive behavior. Initially, we examine modifications in the ventral subiculum-nucleus accumbens (vSub-NAc) pathway, which is implicated in processing of contextual information and motivational function, after exposure to cocaine or after chronic mild stress. (MORE DETAILS)
Alterations in the brain reward pathway persist in depression. An established neurochemical marker associated with neuroplasticity that is altered in depression is brain derived neurotrophic factor (BDNF). Despite the established association between reduced BDNF levels in the hippocampus, reduction in neurogenesis, and depression, it is not known whether reduced BDNF levels can directly precipitate depressive behavior, or are merely a side effect of the disease. We are studying the direct behavioral and neurochemical effects of BDNF knockdown in specific brain regions in-vivo. (MORE DETAILS)
There are many other factors that can cause, intensify, or ameliorate depressive symptoms, and this illness is thought to result from a combination of genetic and environmental factors. In order to study the genetic factors of depressive behavior under controlled conditions we are establishing a novel animal model for depression based on selective breeding for depressive phenotypes. (MORE DETAILS) A key factor in the environmental component of depression is chronic stress. Exposure to chronic mild stress (CMS) is known to induce anhedonia in adult animals, and is associated with the development of depression in humans. We have recently characterized the behavioral effects of CMS in young versus adult animals and measured markers for alterations in neuronal plasticity; mainly changes in BDNF and glutamate receptor levels induced by chronic stress. (MORE DETAILS) To enhance neuroplasticity in animal models for depression, we study the behavioral and neurochemical outcomes of localized brain stimulation, as we do in the addiction studies described above. We test whether sub-convulsive stimulation using intracranial electrical stimulation (ICS) of reward-related brain sites, such as the prelimbic cortex (PLC) or NAC, can affect BDNF levels and induce antidepressant effects in a widely-used rat model for depressive behavior. (MORE DETAILS)
The translation of our animal studies using electrical stimulation in models for addiction and depression to human studies is performed with our newly developed Transcranial Magnetic Stimulation (TMS) coil allowing stimulation of deeper brain regions. In collaboration with clinical centers we test the various effects of repeated treatment with Deep TMS on depressive and addicted subjects. Deep TMS produces directed electromagnetic fields that can induce excitation of neurons in deep brain areas without the need for a surgery. This approach allows the study of the various effects of repeated brain stimulation in humans (MORE DETAILS)