Glutamatergic involvement in psychomotor stimulant action

Abstract

The sympathomimetic psychomotor stimulants, including cocaine, amphetamines, and the phenylethylamine amphetamine-like derivatives, exert actions in mammalian systems that implicate involvement of the excitatory neurotransmitter, glutamate and its receptors. Despite evidence that psychomotor stimulants do not directly stimulate glutamate receptors, blockade of acute lethal, convulsive, circulatory, thermoregulatory, locomotor and stereotypical responses, as well as interference with slowly developing behavioral sensitization and brain monoaminergic neurotoxicities, can be achieved by receptor antagonists at both N-methyl-D-aspartate and AMPA/kainate glutamate receptor subtypes. Alterations in glutamatergic neurobiology, including elevations in extracellular glutamate levels, changes in glutamate receptor properties and glutamatergic neuronal degeneration, have also been attributed to psychomotor stimulant administration. Blockade of glutamate receptors offers therapeutic options in management of psychomotor stimulant toxicity.