CURRICULUM VITAE

THE LABORATORY OF YOSSEF ITZHAK, Ph.D.
	From left to right:   Cindy Achat (Graduate Student, Neuroscience Program), Yossef Itzhak, Ph.D. (Principal Investigator), Karen Anderson MSc. (Research Assistant) Collaborator: Syed F. Ali, Ph.D. (National Centre for Toxocological Research, FDA, Arkansas)

OVERALL GOALS OF OUR RESEARCH

Psychostimulants such as cocaine, amphetamine, methamphetamine (crystal METH) and MDMA (ecstasy) are widely abused substances. Repeated use of METH and MDMA causes the development of severe addiction, aggression, violent and psychotic behavior, memory loss and neurodegeneration of central dopamine and serotonin pathways. The mechanisms underlying the euphoric, addictive and neurotoxic effects of psychostimulants are poorly understood. Also, there are no pharmacotherapies against substituted amphetamines’ addiction and neurotoxicity. Our goals are to: a) to elucidate the neural substrates involved in the effects of psychostimulants and b) to identify potential pharmacotherapies against addiction to psychostimulants. The neural adaptation (e.g. addiction) that occurs following exposure to psychostimulants may involve different neurotransmitter systems. Our focus is on the role of glutamatergic and nitric oxide (NO) systems that play a role in neural plasticity and learning and memory.

We developed behavioral paradigms to investigate the effects of psychostimulants on a) open-field behaviors, b) reward seeking c) learning and memory performance. The behavioral experiments include a comparison between the responses of wild-type and knockout mice to psychostimulants.

In neurochemical experiments, brain dopaminergic and serotoninergic neurotoxicity is being investigated after exposure of mice (wild-type and knockout) to METH and MDMA.

  At the molecular level, the effects of psychostimulants on the expression of glutamate receptor subunits, neuronal nitric oxide synthase (nNOS) and cyclic GMP in limbic brain structures are being investigated.

Radial Arm Maze used to monitor the effect of administration of substances of abuse on learning and memory.

RECENT REFERENCES

PUBLICATIONS

Itzhak Y, Martin JL.Cocaine-induced conditioned place preference in mice: induction, extinction and reinstatement by related psychostimulants. Neuropsychopharmacology.  2002 Jan;26(1):130-4.

Itzhak Y, Martin JL, Ali SF.Comparison between the role of the neuronal and inducible nitric oxide synthase in methamphetamine-induced neurotoxicity and sensitization.
Ann N Y Acad Sci. 2000;914:104-11.

Itzhak Y, Martin JL. Scopolamine inhibits cocaine-conditioned but not unconditioned stimulant effects in mice.Psychopharmacology (Berl). 2000 Oct;152(2):216-23.

Itzhak Y, Martin JL, Ail SF.nNOS inhibitors attenuate methamphetamine-induced dopaminergic neurotoxicity but not hyperthermia in mice. Neuroreport. 2000 Sep 11;11(13):2943-6.

Itzhak Y, Martin JL.Effect of riluzole and gabapentin on cocaine- and methamphetamine-induced behavioral sensitization in mice. Psychopharmacology (Berl). 2000 Aug;151(2-3):226-33.

Martin JL, Itzhak Y.7-Nitroindazole blocks nicotine-induced conditioned place preference but not LiCl-induced conditioned place aversion. Neuroreport. 2000 Apr 7;11(5):947-9.

Itzhak Y, Martin JL.Blockade of alcohol-induced locomotor sensitization and conditioned place preference in DBA mice by 7-nitroindazole. Brain Res. 2000 Mar 10;858(2):402-7.

ABSTRACTS

Achat C., Ali S.F., Itzhak Y. Methamphetamine- and MDMA-induced neurotoxicity: Sensitization to the locomotor stimulating effects and desensitization to the rewarding effects of psychostimulants. College on Problems of Drug Dependence (CPDD), 64^th Annual Scientific Meeting, Quebec, Canada, June, 2002.

Achat C., Anderson K. L., Itzhak Y. MDMA neurotoxicity in mice: Sensitization to locomotor activity and reward-seeking behavior. Annual Meeting, Society for Neuroscience, Orlando, FL, November, 2002.