David Sulzer - Addictive Drugs

Addictive Drugs

By introducing the "weak base hypothesis" of amphetamine action, means to measure amphetamine's effects on the quantal size of dopamine release, intracellular patch electrochemistry to measure dopamine levels in the cytosol, and providing real-time measurement of dopamine release by reverse transport, Sulzer's lab showed how amphetamine and methamphetamine release dopamine and other neurotransmitters and exert their synaptic and clinical effects.

The group extended these findings to show how methamphetamine neurotoxicity occurs, due to dopamine-derived oxidative stress in the cytosol followed by induction of autophagy, and with Nigel Bamford of the University of Washington, how these drugs activate long-term changes in the cortical synapses that project to the striatum: these changes, which they label "chronic postsynaptic depression" and "paradoxical presynaptic potentiation", the latter because methamphetamine selectively normalizes cortical synapses only of animal that previously were exposed to the drugs, appear to last for the life-time of the animal, and may underlie changes in the brain that lead to drug dependence and addiction.