Background and Purpose-In premature infants, many of whom experience ischemic brain insults, the environment of rearing influences cognitive outcome. We developed a model to evaluate the effect of rearing conditions on learning after unilateral cerebral hypoxia-ischemia (HI) in 7-day-old (P7) rats. We hypothesized that neonatal handling would benefit rats recovering from an episode of HI. Methods-Seventeen litters of P7 Long-Evans rats underwent either HI (right carotid ligation followed by 1.5 hours in 8%O 2 ) or control procedures. From P8 to P14, randomized litters were either handled (15 minutes of separation from dam per day) or nonhandled. After P55, learning was tested in the Morris water maze. To evaluate injury severity, hippocampal, cortical, and striatal volumes were measured. Results-In water-maze performance, ANCOVA revealed an interaction between handling and severity of hippocampal damage. Among HI rats, handled rats learned faster when hippocampal damage was moderate (PϽ0.01, repeatedmeasures ANOVA), with no benefit when damage was mild or severe. Conclusions-These observations suggest the beneficial cognitive effect of neonatal handling was limited to animals with moderate damage. Neonatal handling in post-HI rats may be a useful model in which to study mechanisms underlying the benefits of post-HI developmental intervention.

Quantitative receptor autoradiography was used to examine the effect of chronic cocaine exposure on the density of alpha1-, alpha2- and beta-adrenergic, 5-HT1A- and 5-HT2-serotonergic, and D1- and D2-dopaminergic receptors in the fetal guinea pig cerebral wall which contained forming motor area of the cerebral cortex. The pregnant guinea pig received two daily subcutaneous injections of 20 mg/kg cocaine beginning on the 20th day of pregnancy (E20). The control animals received injections of equivalent volume of saline. The receptor densities were examined between days 5-30 of the treatment, which corresponds to E25-E50. By the fifth day of treatment (E25), cocaine produced downregulation of all receptors studied throughout the entire depth of the fetal cerebral wall. More extended treatment, however, resulted in recovery of receptor levels. Finally, from days 20-30 of treatment (E40-E50) there was a significant upregulation of noradrenergic and dopaminergic receptor sites. These findings demonstrate that exposure to cocaine in utero can influence adrenergic, serotonergic, and dopaminergic receptors in the embryonic cerebral wall, which may lead to alteration in corticogenesis. Furthermore, the present study reveals that, in the course of chronic treatment, cocaine may completely reverse its receptor regulatory activity in the fetal brain.