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.
Singh
N A
NA
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112.
Midgley
L P
LP
Bush
L G
LG
Gibb
J W
JW
Hanson
G R
GR
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