Psychostimulants, Madness, Memory... and RGS Proteins?

Abstract

The ingestion of psychostimulant drugs by humans imparts a profound sense of alertness and well-being. However, repeated use of these drugs in some individuals will induce a physiological state of dependence, characterized by compulsive behavior directed toward the acquisition and ingestion of the drug, at the expense of customary social obligations. Drugs of abuse and many other types of experiences share the ability to alter the morphology and density of neuronal dendrites and spines. Dopaminergic modulation of corticostriatal synaptic plasticity is necessary for these morphological changes. Changes in the density of dendritic spines on striatal neurons may underlie the development of this pathological pattern of drug-seeking behavior. Identifying proteins that regulate dopaminergic signaling are of value. A family of proteins, the regulators of G protein signaling (RGS) proteins, which regulate signaling from G protein-coupled receptors, such as dopamine and glutamate, may be important in this regard. By regulating corticostriatal synaptic plasticity, RGS proteins can influence presynaptic activity, neurotransmitter release, and postsynaptic depolarization and thereby play a key role in the development of this plasticity. Pharmacological agents that modify RGS activity in humans could be efficacious in ameliorating the dependence on psychostimulant drugs.