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 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 D1 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 D1 and glutamate NMDA receptors.
Hanson
G R
GR
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112, USA.
Singh
N
N
Merchant
K
K
Johnson
M
M
Gibb
J W
JW
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000378:metabolism; D008694:Methamphetamine / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009479:Neuropeptides / Q000378:metabolism*; D009496:Neurotensin / Q000378:metabolism; D009714:Nucleus Accumbens / Q000187:drug effects*; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D009479:Neuropeptides; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D009496:Neurotensin; D008694:Methamphetamine; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D004399:Dynorphins; D003042:Cocaine