Association of nerve growth factor mRNA levels with MK-801-induced explosive behaviors in mice

MK-801, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, stimulated an outbred strain of NIH Swiss mice to display discrete episodes of explosive jumping behavior, designated as "popping." The rapid onset of the MK-801-induced "popping" seems to follow the rapid distribution of the drug to the frontal cortex, the area that contains high levels of NMDA receptors. We examined the effect of this drug on the levels of mRNA coding for nerve growth factor (NGF) in the frontal cortex in relation to the exhibited "popping" episodes. Mice treated with 1 mg/kg MK-801 could be split into two groups based on the total number of "popping" episodes in a 30 min post-injection period. These groups also differed in the steady-state levels of frontal cortex NGF mRNA. Animals that exhibited low numbers of "popping" had levels of NGF mRNA significantly higher than saline treated controls or mice that exhibited high numbers of "popping." Mice treated with 10 mg/kg MK-801 had a high frequency of "popping" that was impossible to separate into episodes. In addition, these mice had levels of frontal cortex NGF mRNA that were significantly lower than either group of mice treated with 1 mg/kg MK-801. These data indicated that there was an increased level of NGF mRNA under conditions where MK-801 induced a low level of "popping" behavior. However, when "popping" intensified, NGF mRNA levels were decreased, suggesting a possible behavioral antagonism of the NGF response.