Effects of psychomotor stimulants on glutamate receptor expression.

It is increasingly well accepted that addiction can be viewed as a form of neuronal plasticity, even as a type of very powerful, albeit maladaptive, learning. On a behavioral level, this can be conceptualized as the transition from experimentation to compulsive drug-seeking behavior. This view of addiction has been strengthened by many recent studies demonstrating commonalities between mechanisms underlying learning and addiction. Both are associated with changes in gene expression, phosphorylation and phosphatase cascades, neurotrophin signaling, altered dendritic morphology, and activity-dependent forms of plasticity such as long-term potentiation (LTP) and long-term depression (LTD) (1,2). Through these mechanisms, drugs of abuse are proposed to strengthen or weaken activity in pathways related to motivation and reward. This in turn may produce behavioral changes that drive compulsive drug-seeking behavior in addiction, including sensitization of incentive-motivational effects of drugs, enhanced ability of drug-conditioned stimuli to control behavior, and loss of inhibitory control mechanisms that normally govern reward-seeking behavior (3,4). An open question is how drugs of abuse, which initially target monoamine receptors, are able to infl uence mechanisms of synaptic plasticity. Glutamate is a key transmitter for synaptic plasticity, and many neuronal pathways implicated in addiction are glutamatergic (4). Historically, studies of behavioral sensitization, a well-established animal model for addiction, were important in directing drug addiction research toward glutamate (5). Behavioral sensitization