Repeated reserpine increases striatal dopamine receptor and guanine nucleotide binding protein RNA.
In the present study the effects of repeated administration of reserpine on striatal dopamine receptor and guanine nucleotide binding protein mRNAs were determined. Twenty-four hours after seven consecutive daily injections of reserpine--a treatment that is known to produce functional sensitization of D1 and D2 dopamine receptors--the level of striatal D1 dopamine receptor mRNA was unchanged. However, the level of mRNA for the G protein Gs alpha was increased by 127%. After extended reserpine treatment for 14 days, levels of both striatal D1 DA receptor and Gs alpha mRNAs were elevated by 99 and 78%, respectively. Seven days of reserpine treatment also increased levels of mRNA of the striatal D2 dopamine receptor and of G proteins Gi2 alpha and Go alpha by 200, 79, and 32%, respectively. After 14 days of reserpine treatment the level of striatal D2 dopamine receptor mRNA was increased by twofold. In contrast, levels of the mRNAs coding for the G proteins Gi2 alpha and Go alpha were unchanged. These data suggest that dopamine receptors and their respective G proteins play important roles in the development of sensitization of striatal dopamine receptors during repeated reserpine treatment. Furthermore, the persistent increase in level of striatal Gs alpha mRNA suggests that this G protein is necessary to maintain supersensitivity of the striatal D1 dopamine receptor system following long-term dopamine depletion.
Butkerait
P
P
Department of Psychiatry, Medical College of Pennsylvania, EPPI, Philadelphia 19129.
Friedman
E
E
D000818:Animals; D015152:Blotting, Northern; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D015342:DNA Probes; D004298:Dopamine / Q000378:metabolism*; D004334:Drug Administration Schedule; D019204:GTP-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000096:biosynthesis* / Q000235:genetics; D017447:Receptors, Dopamine D1 / Q000096:biosynthesis / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis / Q000235:genetics; D012016:Reference Values; D012110:Reserpine / Q000008:administration & dosage / Q000494:pharmacology*; D015183:Restriction Mapping; D013997:Time Factors
D015342:DNA Probes; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012110:Reserpine; D019204:GTP-Binding Proteins; D004298:Dopamine