N-Methyl-D-aspartate receptors mediate dopamine-induced changes in extrapyramidal and limbic dynorphin systems.
The N-methyl-D-aspartate (NMDA)-type glutamate receptor was shown to mediate dopamine-induced dynorphin A (Dyn) changes in extrapyramidal and limbic structures. MK801, a potent noncompetitive antagonist of the NMDA receptor, blocked increases in striatal and nigral Dyn content following single and multiple administrations of methamphetamine (METH). Significant attenuation of the METH-induced increases occurred with MK801 doses of 0.1 mg/kg/dose with complete blockade at 2.5 mg/kg/dose. Similar to METH, NMDA itself caused significant increases in striatal and nigral Dyn content. The NMDA-induced increase in striatal Dyn content was blocked by coadministration of an intermediate dose of MK801. The Dyn system associated with the nucleus accumbens responded in a similar manner in that MK801 totally blocked the METH-induced increases; moreover, NMDA elevated the Dyn content in this structure. The inability of MK801 to alter the quinpirole-induced decrease in striatal Dyn content suggests that the NMDA receptor is not involved in the D2 receptor regulation of striatal Dyn systems.
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112.
N A
NA
Singh
L P
LP
Midgley
L G
LG
Bush
J W
JW
Gibb
G R
GR
Hanson
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D004399:Dynorphins / Q000502:physiology*; D005116:Extrapyramidal Tracts / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008032:Limbic System / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D008694:Methamphetamine; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D004399:Dynorphins; D004298:Dopamine