Acute Systemic Neonatal Protein Synthesis Inhibition

The early postnatal period represents a time of significant neural development. Neonatal exposure to stressors, environmental toxins, and many different pharmacological agents may have a significant impact on subsequent behavior and cognition in adulthood. The purpose of this study was to examine the effects of early administration of the protein synthesis inhibitor, cycloheximide, on a battery of behavioral and cognitive tests in adulthood. Twelve-day-old Sprague-Dawley rats were administered saline or .5 mg/kg of cycloheximide subcutaneously. Upon reaching adulthood, a battery of tests were administered in order to examine anxiety, locomotor activity, environmental habituation, spatial working memory, object recognition memory, long-term spatial memory, and conditioned taste aversion. Most tests failed to reveal any differences between postnatally exposed cycloheximide and saline animals. However, during the water maze probe test, cycloheximide exposed animals reached the original platform location significantly faster than saline controls. For the conditioned taste aversion test, during the initial exposure to a 10% sucrose solution (prior to the induction of the taste aversion) the cycloheximide animals consumed significantly more than saline controls, indicating an attenuation of neophobia. Although acquisition of a conditioned taste aversion was comparable in neonatally exposed cycloheximide and saline animals, there was a significant resistance to extinction by cycloheximide animals. These results suggest that animals exposed to cycloheximide on postnatal day 12 displayed enhanced long-term spatial memory, reduced neophobia, and enhanced memory for taste aversion conditioning as indicated by a resistance to extinction.