The role of NMDA receptor systems in neuropeptide responses to stimulants of abuse

Abstract High doses of stimulants of abuse, such as methamphetamine and cocaine, cause significant increases in the content of neurotension- and dynorphin-like immunoreactivity in the striatum and nucleus accumbens (approximately 200–600% of control) in the rat. These changes in neuropeptide content are caused by stimulation of dopamine D 1 receptors and prevented by the glutamate NMDA receptor antagonist, MK 801. Stimulation of the NMDA receptor with N -methyl- d -aspartate results in increases in the neuropeptide levels like that caused by methamphetamine and cocaine. These findings demonstrate that stimulants of abuse profoundly influence neurotensin and dynorphin pathways associated with extrapyramidal and limbic structures by an interaction of activated dopamine D 1 and glutamate NMDA receptors.