Sershen Lab

The Sershen Lab has a long-term publication record in studying the mechanism of action of stimulant drugs, and ours was one of the earliest groups to characterize the binding properties of nicotine and cocaine in brain.

We have explored the interaction of early adolescent drug exposure on subsequent response. Notably, we have found differences in serotonin responses in the adolescent that may be responsible for their differences in drug reward compared to adults, and potentially involved in the increased risk to subsequent drug seeking behavior.

We have also characterized the heterogeneity of drug-reward responses to different drugs of abuse, as well as food-reward.

Effect of Stimulants on the Brain

One of our lab’s major interests has been to characterize the properties of action of cocaine, nicotine, and other stimulants in brain. Recently, our aim has been to identify the multiplicity, heterogeneity, and specificity of transmitter changes that occur with psychostimulant use; the effect of use of stimulants in adolescent rodents on subsequent responses in adult rodents; and the interaction of nicotine in schizophrenia.

Neurofilaments and Receptors

Studies are also ongoing to investigate the role of neurofilaments in regulating the expression of dopamine, NMDA, and nicotinic receptors. Besides having a role in axon caliber and cytoskeleton structure, neurofilaments appear to have a role in the trafficking and cell surface expression of receptors. These studies are being done in collaboration with the Nixon Lab at NKI.

Receptors and Schizophrenia

We are also investigating neurotransmitter receptors and schizophrenia. In collaboration with Dr. Daniel Javitt, we have further identified and characterized the function of NMDA receptors in this disease. Ongoing studies are aimed at modulating this site in attempts to affect treatment outcomes.

Although targeting the co-agonist site of the NMDA receptor shows promise, at present its actions are only effective in animal models. Studies are still ongoing to further clarify the function/modulation of the co-agonist site of the NMDA receptor as it may apply to treatment modalities.

Collaborating with Dr. Robert Smith, we have been studying potential epigenetic changes in genes involved in schizophrenia, and their modulation, for example by smoking or direct current stimulation (tDCS). The study is evaluating the role of DNMTmRNA (hypofunction) as it relates to schizophrenia, by testing whether peripheral lymphocytes can model brain changes in several populations of schizophrenic patients, and to see whether there is a relationship between DNMTmRNA and smoking in these patients.