Drug addiction: Knockout mice and dirty drugs

نویسندگان

George R. Uhl

David J. Vandenbergh

Lucinda L. Miner

چکیده

The addictive drugs cocaine and amphetamine stimulate locomotion and provide behavioral reward. They have multiple molecular sites of action, of which those on sodiumand chloride-dependent neurotransmitter transporters are thought to be particularly important [1,2]. Both drugs bind to the plasma-membrane transporters for dopamine, norepinephrine and serotonin, inhibiting reuptake into neurons of each of these monoamines. Amphetamine can also disrupt the hydrogen ion gradient across the membranes of the synaptic vesicles that store monoamines, releasing them into the cytoplasm from where they can be exported out of the cell by mechanisms suggested to include ‘reverse’ transport by the plasma-membrane transporters [3]. Cocaine also blocks voltage-gated sodium channels at higher concentrations [4]. These wide-ranging effects make cocaine and amphetamine prototypical ‘dirty drugs’, and have led to persistent uncertainties about which sites contribute to their locomotor effects and which to their rewarding behavioral actions.

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