Grant: Operating Grant

Sensitization to amphetamine, a drug of abuse commonly referred to as "speed" is a phenomenon resulting in an individual experiencing, after some time, when being again exposed to the drug, a heightened response to the drug, despite the fact that the dose remained unchanged. This process is often long lasting and more likely to develop when the drug is repeatedly administered within the same environment. It works as some form of intrinsic memory, hard wired in brain cells, particularly those using the neurotransmitter dopamine, and recalled at re-exposure with some amplification of effects. This process also occurs upon exposure to repeated stress. It is believed to play a role in why certain individuals develop craving for some of the effects of drugs, hence abuse them or why others become increasingly vulnerable to the consequences of stress, to the point of developing catastrophic reactions to subsequent aversive events, which, in some cases, may trigger the onset or relapse of various forms of mental illness. The proposed application has two main objectives: the most important is to build on progress, made during the past 5 years,to unravel the mechanisms at play during sensitization. Experiments are designed to study whether sensitization to stimulants involves stable changes of brain chemicals other than dopamine and brain circuits other than the basal ganglia. The second objective of the application, expands the scope of the research towards other forms of brain plasticity, for which long term changes in the hard wiring and functioning of brain chemicals, in response to negative environments, biases emotion regulation and perturbs behavior. Emphasis here will be on the conditioning to fear, experienced in the face of trauma.