THE ROLE OF NMDA RECEPTOR SYSTEMS IN NEUROPEPTIDE RESPONSES TO STIMULANTS OF ABUSE

High doses of stimulants of abuse, such as methamphetamine and cocaine , cause significant increases in the content of neurotension- and dyno rphin-like immunoreactivity in the striatum and nucleus accumbens (app roximately 200-600% of control) in the rat. These changes in neuropept ide content are caused by stimulation of dopamine D-1 receptors and pr evented by the glutamate NMDA receptor antagonist, MK 801. Stimulation of the NMDA receptor with N-methyl-D-aspartate results in increases i n the neuropeptide levels like that caused by methamphetamine and coca ine. These findings demonstrate that stimulants of abuse profoundly in fluence neurotensin and dynorphin pathways associated with extrapyrami dal and limbic structures by an interaction of activated dopamine D-1 and glutamate NMDA receptors.