Abel Lajtha, M.D., Director

Dr. Lajtha and collaborators among others, Drs. Henry Sershen and David Dunlop, with A. Hashim, S. Rossi, S. Singer, S. Verzosa, E. Shearman, and S. Fallon, present projects focusing on the role of neurotransmitter systems in reward and cognitive mechanisms. Reward mechanisms represent the major driving force in behavior, including drug abuse, which is: addiction, but also activities that are pleasurable such as: feeding, and sexual activity, and activities that represent stress that indicate negative reward. In addition, reward mechanisms involve processes of learning. The group also studies the role of neurotransmitter systems in learning and memory - these mechanisms in turn involve processes of reward. In this respect although reward and learning represent two different functions, they also interact and are interlinked.

Dr. Lajtha, with collaborators, examine the neurotransmitter changes in brain structures involved in learning caused by stimulants such as caffeine, drugs used for therapy for Alzheimer's patients, and compounds reported to enhance memory. As neurotransmitter changes are established, with the help of specific neuroreceptor subtype antagonists, the specific receptors responsible for the changes can be identified. Many of these studies, and the studies measuring the effect of the drugs on learning, are done on conscious, freely moving rodents. Drug administration in specific brain structures is used to identify the role such structures play in neurotransmitter reactions.

The focus of studies of reward is neurotransmitter changes induced by drugs of abuse, examining the different patterns of the effects of different drugs and the risk factors that influence drug abuse. The effects of nicotine, and the possible therapeutic use of nicotinic compounds in mental illness, are of special interest to the laboratory. One project examines the effects of smoking on schizophrenic patients, in collaboration with Dr. Robert Smith at the Manhattan Psychiatric Center. The laboratory collaborates on special projects with Drs. Janos Kiss and Sylvester Vizi of the Institute for Experimental Medicine of the Academy of Sciences in Budapest, and in examining neuroreceptor-related changes in Alzheimer's patients, with Dr. Nunzio Pomara at the Nathan Kline Institute.

Reward processes are compared in adolescent versus adult animals (adolescents are more prone to addiction) learning processes are compared in adult versus ________ animals. Also strain differences in sensitivity for addiction or in learning are used to examine changes in neurotransmitters that play a major role in reward or in learning.

Peptide Research Laboratory

The Peptide Research Laboratory studies the neurochemistry underlying mental health and disease by examining brain-specific proteins and neuropeptide metabolism. Brain-specific proteins are pivotal biomarkers and powerful tools for studying of neural mechanisms and neuropathology. Their functions have been identified in neurotransmitter metabolism, cell-to-cell recognition, differentiation, signal transduction, glycolysis, gene expression, receptors, ion channels, and the cytoskeleton.

Laboratory of Neuronal Cell Death Mechanisms

The Laboratory of Neuronal Cell Death Mechanisms is examining roles for death effector caspases as moderators in isolated primary neurons or neuroblastoma N2a as models following treatment with apoptotic or necrotic stressors. The lab also focuses on roles of other cysteine proteases of lysosomal origin including cathepsins B and L as well as peptidases known as secretases implicated in the turnover of the Alzheimer's amyloid precursor protein that yield the amyloid peptide characteristic of extracellular lesions. These enzymes appear to also take part in numerous signaling pathways and have general function in maintaining cellular homeostasis. Here we investigate their characterization and specificity using various cell biological techniques such as enzymology, microscopy and imaging and innovative approaches involving gene silencing.

Selected Publications

Javitt. D.C., Balla, A., Sershen. H., and Lajtha, A. "Reversal of Phencyclidine-Induced Effects by Glycine and Glycine Transport Inhibitors." BioI. Psychiat. 45, 668-679 (1999).

Javitt. D.C., Sershen. H., Hashim, A., and Lajtha, A. "Inhibition of Striatal Dopamine Release by Glycine and Glycyldodecylamide." Brain Res. Bull. 52.213-216 (2000).

Sershen. H., Hashim. A., and Lajtha, A. "Serotonin-Mediated Striatal Dopamine Release Involves the Dopamine Uptake Site and the Serotonin Receptor." Brain Res. Bull. 53,353-357 (2000).

Sziráki, I., Lipovac, M.N., Hashim, A., Sershen. H., Allen. D., Cooper. T., Czobor, P., and Lajtha. A. "Differences in Nicotine-Induced Dopamine Release and Nicotine Pharmacokinetics between Lewis and Fischer 344 Rats." Neurochem. Res. 26: 609-617 (2001).

Balla, A., Hashim. A., Burch, S., Javitt. D.C., Lajtha, A., and Sershen. H. "Phencyclidine-Induced Dysregulation of Dopamine Response to Amphetamine in Prefrontal Cortex and Striatum." Neurochem. Res. 26: 1001-1006 (2001).

Sziráki, I., Sershen. H., Hashim, A., and Lajtha, A. "Receptors in the Ventral Tegmental Area Mediating Nicotine-Induced Dopamine Release in the Nucleus Accumbens." Neurochem. Res. 27: 253-261 (2002).

Pomara, N., Willoughby, L.M., Hashim, A., Sershen, H., Sidtis, J.J., Wesnes, K., Greenblatt, D.J., and Lajtha, A. "Effects of Acute Lorazepam Administration on Aminergic Activity in Normal Elderly Subjects: Relationship to Performance Effects and Apolipoprotein Genotype." Neurochem. Res. 29: 1391-1398 (2004).

Singer, S., Rossi, S., Verzosa, S., Hashim, A., Lonow, R., Cooper, T., Sershen, H., and Lajtha, A. "Nicotine-Induced Changes in Neurotransmitter Levels in Brain Areas Associated with Cognitive Function." Neurochem Res. 29: 1779-1792 (2004).

Rossi, S., Singer, S., Shearman, E., Sershen, H., and Lajtha, A. The Effects of Cholinergic and Dopaminergic Antagonists on Nicotine-Induced Cerebral Neurotransmitter Changes. Neurochem. Res. 30: 541-558 (2005).

Shearman, E., Rossi, S., Sershen, H., Hashim, A. and Lajtha, A. Locally Administered Low Nicotine-Induced Neurotransmitter Changes in Areas of Cognitive Function. Neurochem. Res. 30: 1055-1066 (2005).

Shearman, E., Rossi, S., Szasz, B., Juranyi, Z., Fallon, S., Pomara, N., Sershen, H., and Lajtha, A. Changes in Cerebral Neurotransmitters and Metabolites Induced by Acute Donepezil and Memantine Administrations: A Microdialysis Study. Brain Research Bulletin 69: 204-213 (2006).

Fallon, S., Shearman, E., Sershen, H., and Lajtha, A. The Effects of Glutamate and GABA Receptor Antagonists on Nicotine-Induced Neurotransmitter Changes in Cognitive Areas. Neurochem. Res. 32: 535-553 (2007).

Fallon, S., Shearman, E., Sershen, H., and Lajtha, A. Food Reward Induced Neurotransmitter Changes in Cognitive Brain Regions. Neurochem. Res. (in press, 2007) DOI: 10.1007/s11064-007-9343-8

For further information, contact Dr. Lajtha at