Effects of Psychomotor Stimulants on Glutamate Receptor Expression - Drugs of Abuse: Neurological Reviews and Protocols - page 11

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Effects of Psychomotor Stimulants
on Glutamate Receptor Expression
Marina E. Wolf
1. Introduction: Addiction as a Form
of Glutamate-Dependent Plasticity
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 depres-
sion (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