Paradoxical effects of ketamine on the memory of fetuses of different ages

Abstract

Brain N-methyl- d-aspartate (NMDA) glutamate receptors have been implicated as important mediators of both learning and neuronal development. The current study investigated how ketamine (a well-known NMDA-receptor blocking drug) influences taste-mediated conditioned motor responses (CMRs) in perinatal rats. Dams pregnant with either embryonic day 18 (E18) or E19 rat fetuses were injected with 0 or 100 mg/kg ketamine HCl (i.p.). One-half hour later, a reversible spinal block was performed on the dam and fetuses received oral lavage with 10 μl, 0.3% saccharin (SAC) or water (control) in utero. After the oral injection, fetuses received either a saline (control) or lithium chloride (LiCl) injection (81 mg/kg, i.p.). The uterus was replaced and, 2 days later (E20 or E21), some rats received oral lavage with SAC. Other litters were born via normal vaginal delivery or Cesarean section and orally exposed to SAC on post-natal day 3 (P3). Motor responses were observed immediately after the oral lavage of SAC. If SAC had been paired with LiCl in utero, pups generally exhibited conditioned suppression of orofacial movements (as compared to controls). Ketamine significantly attenuated this taste-mediated CMR of animals conditioned on E19. However, the same treatments did not disrupt CMRs of rats treated with ketamine before CS–US pairing on E18. Our findings indicate an age-dependent role for NMDA receptors in the formation of CMRs in perinatal rats.