PREPROTACHYKININ AND PREPROENKEPHALIN MESSENGER-RNA EXPRESSION WITHINSTRIATAL SUBREGIONS IN RESPONSE TO ALTERED SEROTONIN TRANSMISSION

The effects of lowered serotonin (5-hydroxytryptamine; 5-HT) neurotran smission on preprotachykinin (PPT) and preproenkephalin (PPE) mRNA lev els were examined in subregions of the striatum. Adult male rats were treated systemically with para-chlorophenylalanine (pCPA, 350 mg/kg si ngle i.p. injection) which reduced forebrain 5-HT amounts to approxima tely 20% of saline-injected controls at 24 and 48 h. As measured by No rthern analysis, PPT and PPE mRNA levels were elevated 50% and 160% re spectively in the anterior ventromedial striatum (region included nucl eus accumbens). PPT mRNA levels were raised 90% in posterior striatum (at the level of the globus pallidus) by 48 h post-pCPA injection. To determine if increased PPT and PPE mRNA levels represented a transient response to brief 5-HT inhibition, additional experiments were perfor med to provide continual suppression of 5-HT within the striatum. Firs t, rats received daily intraperitoneal injections of saline or the 5-H T1A receptor agonist, 8-OK-DPAT (1 mg/kg), for 7 days to reduce 5-HT r elease from raphestriatal terminals. In a parallel experiment, the ser otonin neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT, 5 mu g), was ster eotaxically injected into the striatum as a means to permanently remov e 5-HT terminals. Although levels of each mRNA species were differenti ally sensitive to 5,7-DHT or 8-OH-DPAT, PPT and PPE mRNAs were lowered between 30-55% within the anterior dorsolateral and ventromedial stri atum. Although these results support previous studies suggesting an ov erall positive regulatory role of serotonin on striatal tachykinin bio synthesis. PPT and PPE gene regulation in certain striatal subregions may be differentially sensitive to lowered 5-HT neurotransmission. Thi s suggestion is supported by observations that acute systemic stimulat ion of 5-HT2A/C receptors with DOI (7 mg/kg single i.p. injection) rai sed PPT and PPE mRNA levels within anterior dorsolateral (30-60%) and posterior (100-200%) striata, but not within the anterior ventromedial striatum.