Ketamine blocks a taste-mediated conditioned motor response in perinatal rats

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 HCl (a well-known NMDA-receptor blocking drug) would influence taste-mediated conditioned motor responses in perinatal rats. Dams pregnant with E19 rat fetuses were injected with 0, 50, or 100 mg/kg ketamine HCl (IP). One-half hour later, a reversible spinal block was performed on the dam, and fetuses received an oral injection of 10 microl 0.3% Saccharin (SAC) or water while in utero. After the oral injection, fetuses received either saline or LiCl (81 mg/kg, IP). The uterus was replaced and, 2 days later (E21), rats received oral lavage with SAC. Rats in other litters were born via a normal vaginal delivery and were exposed to SAC on postnatal day 3 (P3). Observations of motor responses were recorded immediately after the oral lavage of SAC. If SAC had been paired with LiCl in utero, both E21 and P3 pups exhibited a conditioned suppression of orofacial movements (compared to controls). Both doses of ketamine significantly attenuated this taste-mediated conditioned motor response. These data reinforce the current conception of the fetus and neonate as sophisticated sensors and responders to the uterine and extrauterine environment. Further, our findings indicate a role for NMDA receptors in the formation of a conditioned motor response in fetal rats.