Neurochemical development of the raphe after continuous prenatal cocaine exposure

Disorders among cocaine-exposed infants suggest the medullary raphe nuclei (MRN) as potential targets for cocaine-induced disabilities. Serotonin (5-HT) and substance P (SP) are colocalized within neurons of the MRN. To determine possible neurochemical abnormalities resulting from prenatal cocaine exposure, we measured levels of mRNA coding for the SP preprohormone preprotachykinin (PPT), SP peptide levels, and tryptophan hydroxylase (TPH) activity throughout perinatal and early postnatal development. Pregnant rats at embryonic day 7 (E7) were implanted (SC) with Alzet osmotic minipumps dispensing 10 or 40 mg/kg cocaine daily for 2 weeks. Maternal weight gain, duration of pregnancy, and fetal viability were unaffected by the treatment. Moreover, TPH activity and levels of PPT mRNA [assessed from day E17 through postnatal day (PND) 14] were normal in pups receiving either dose. Except for a transient decline at PND1, SP peptide levels in the ventral spinal cord in the first postnatal week were also unchanged. These data suggest that continuous exposure throughout gestation to these concentrations of cocaine has negligible consequences for the development of these neurotransmitters.