M. Behnam Ghasemzadeh, Ph.D. Research Lab

M. Behnam Ghasemzadeh, Ph.D.

Research in my laboratory focuses on understanding the neurobiology of addiction and schizophrenia. These pathologies involve long-lasting changes in brain function and behavior with devastating personal and social consequences. We are interested in elucidating the cellular and molecular mechanisms underlying these enduring behavioral modifications. Research techniques employed in these studies range from behavioral and neuropharmacological manipulations to cellular and molecular methodologies.

Addiction to drugs of abuse is a major social problem affecting millions of Americans with an overall cost of half a trillion dollars annually. Repeated exposure to psychostimulants such as amphetamine and cocaine produce behavioral modifications which are accompanied by specific changes in neurotransmission and synaptic function in the brain. These changes are long-lasting and thought to underlie the addicted state. However, the causes and consequences of these cellular and molecular plasticity are not fully understood. Glutamate is an excitatory neurotransmitter in the brain that is implicated in the pathologies of addiction. Recent work in my laboratory has focused on cocaine-mediated plasticity in glutamate receptors and intracellular signaling. Using animal models of addiction such as behavioral sensitization and drug self-administration, we have demonstrated selective and region-specific plasticity in glutamate receptor trafficking after exposure to cocaine. In addition, our data indicate that a family of postsynaptic scaffolding proteins are also affected by cocaine. Interestingly, these proteins bind to and regulate glutamate receptor function at the synapse. The goal of this research is to better understand addiction-related plasticity in glutamate signaling in the brain and identify promising pharmacological targets for therapeutic development.

Schizophrenia is a psychiatric disorder that affects about 1% of the world population (more than 2.4 million individuals in US) with long-lasting behavioral consequences. The disease is manifested by a set of abnormal behaviors including psychosis, social withdrawal, and cognitive deficits. These behavioral modifications are accompanied by specific changes in brain structures, neurotransmission and synaptic signaling. Despite more than 50 years of research, the underlying causes are not well understood and there is no cure. Current medications (with annual global sales of $20 billion) are not effective in treating major symptoms such as cognitive deficits and produce serious debilitating side effects such that about 75% of patients become noncompliant after 18 months of treatment. Research in our lab employs animal models of schizophrenia to investigate the cellular and molecular mechanism involved in this brain pathology. We have identified a novel brain mechanism capable of reversing the behavioral abnormalities and cognitive deficits present in animal models of schizophrenia. Importantly, clinical studies suggest that pharmacological manipulation of this mechanism does not produce significant side effects in humans. Current research focuses on better understanding the mechanism of action of this novel brain target using animal models and development of new medications. The goal of this research is to develop and characterize new pharmacological therapies for schizophrenia that can be advanced into clinical trials.

Selected Publications

  • Ghasemzadeh, M.B., Mueller, C.R., Vasudevan, P. (2009) Behavioral sensitization to cocaine is associated with increased glutamate receptor trafficking to the postsynaptic density after extended withdrawal period. Neuroscience. 159: 414-426.
  • Ghasemzadeh, M.B., Vasudevan, P., Mueller, C.R., Seubert, C., Mantsch, J.R. (2009) Region specific alterations in glutamate receptor expression and subcellular distribution following extinction of cocaine self-administration. Brain Research. 1267: 89-102.
  • Ghasemzadeh, M.B., Vasudevan, P., Mueller, C.R. (2009) Locomotor sensitization to cocaine is associated with distinct pattern of glutamate receptor trafficking to the postsynaptic density in the prefrontal cortex: early versus late withdrawal effects. Pharmacology, Biochemistry and Behavior. 92: 383-392.
  • Ghasemzadeh, M.B., Vasudevan, P., Mueller, C.R., Seubert, C., Mantsch, J.R. (2009) Neuroadaptations in the cellular and postsynaptic group1 metabotropic glutamater receptor mGluR5 and Homer proteins following extinction of cocaine self-administration. Neuroscience Letters. 452: 167-171.
  • Ghasemzadeh, M.B., Windham, L.K., Lake, R.W., Acker, C.J., Kalivas, P.W. (2009) Cocaine activates Homer1 immediate early gene transcription in the mesocorticolimbic circuit: differential regulation by dopamine and glutamate signaling. Synapse. 63: 42-53.
  • Ghasemzadeh, M.B., Permenter, L.K., Lake, R., Worley, P.F., Kalivas, P.W. (2003) Homer1 proteins and AMPA receptors modulate cocaine-induced behavioral plasticity. Eur J Neurosci. 18:1645-51.
  • Kalivas, P.W., Toda, S., Bowers, M.S., Baker, D.A., Ghasemzadeh, M.B. (2003) The temporal sequence of changes in gene expression by drugs of abuse. Methods Mol Med. 79:3-11.
  • Crespo, J.A., Oliva, J.M., Ghasemzadeh, M.B., Kalivas, P.W., Ambrosio, E. (2002) Neuroadaptive Changes in NMDAR1 gene expression after extinction of cocaine self-administration. Annals New York Academy Science. 965:78-91.
  • Ghasemzadeh, M.B., Nelson, L., Lu, X-Y., Kalivas, P.W. (1999) Neuroadaptations in ionotropic and metabotropic glutamate receptor mRNA produced by cocaine treatment. Journal of Neurochemistry. 72:157-165.
  • Ghasemzadeh, M.B., Pierce, R.C., Kalivas, P.W. (1999) The monoaminergic neurons of the rat brain preferentially express a splice variant of a1B subunit of the N-type calcium channel. Journal of Neurochemistry. 73:1718-1723.