Serotonin 2A and 2C receptor biosynthesis in the rodent striatum during postnatal development: mRNA expression and functional linkage to neuropeptidegene regulation

The present study was designed to determine if there are region-specific di fferences in serotonin (5-HT) neurotransmission and 5-HT receptor expressio n that may limit the stimulatory effects of the 5-HT releaser p-chloroamphe tamine (pCA) on striatal neuropeptide gene expression to the posterior stri atum (P-STR) during postnatal maturation. Sprague-Dawley rat brains from po stnatal days (PND) 1-35 were processed for 5-HT2A and 5-HT2C receptor mRNA expression by in situ hybridization and monoamine analysis by HPLC. Within the P-STR, 5-HT2A receptor mRNA expression reached young adult (PND 35) lev els by PND 3, while levels in the A-STR were significantly less (range: 1.4 3 +/- 0.219-6.36 +/- 0.478) than P-STR (5.36 +/- 0.854-12.11 +/- 1.08) at e ach respective age throughout the time course. 5-HT2C receptor mRNA express ion reached young adult levels at PND 7 in the A-STR and by PND 3 in the P- STR. At each PND age 5-HT2C receptor mRNA levels within the P-STR were sign ificantly less (6.23 +/- 1.02-12.32 +/- 0.427) than the A-STR (7.31 +/- 1.6 5-26.84 +/- 2.24). 5-HT content increased across the developmental time cou rse within the P-STR (5.01 +/- 0.327-15.7 +/- 1.03 ng/mg protein) and A-STR (2.97 +/- 0.223-11.2 +/- 0.701 ng/mg protein). Four hours following inject ion (i.p.) of pCA (10 mg/kg), preprotachykinin (PPT) mRNA levels increased 89% in the P-STR but not the anterior (A-STR) striatum of the 3-week-old ra t, which were prevented by preinjection (30 min, i.p.) of the 5-HT2 recepto r antagonist ritanserin (1 mg/kg). Together, these data suggest that faster maturity of 5-HT2A receptor expression in the P-STR may be sufficient to c onvey the region-specific acute stimulatory effects of pCA on PPT mRNA tran scription in the developing rodent striatum. These results provide further evidence that the influence of 5-HT on neuropeptide gene expression is far stronger in caudal vs. rostral striatal regions during postnatal developmen t. (C) 2000 Wiley-Liss, Inc.