Now, however, perceptions may shift—not that dopamine descends from the firmament, but that glutamate will sparkle as brightly. Recent knockout mouse evidence1 from researchers led by François Conquet, CEO of Addex Pharmaceuticals in Geneva, Switzerland, reveals that glutamate's role in cocaine dependence is even more central than dopamine's.
The case for dopamine's centrality remains airtight. Cocaine binds the dopamine transporter, blocking reuptake of dopamine into presynaptic neurons. Blockade increases dopamine concentration in synapses, an event responsible for cocaine's pleasurable effects and suggested as key to developing drug dependence. But although loss of the transporter and dopamine receptors in knockout mice may alter behavior toward cocaine, always the drug remains addictive. When the dopamine transporter is lost, for instance, mice may still become cocaine dependent through cocaine's ability to bind the serotonin transporter. This is not necessarily surprising, observes Peter Kalivas, of the Medical University of South Carolina in Charleston, who ...
