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 G(s)alpha was increased by 127%. After extended reserpine treatment for 14 days, levels of both striatal D1 DA receptor and G(s)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 G(i2)alpha and G(o)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 G(i2)alpha and G(o)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 G(s)alpha mRNA suggests that this G protein is necessary to maintain supersensitivity of the striatal D1 dopamine receptor system following long-term dopamine depletion.