Long-term changes in rat social behavior following treatment with trimethylolpropane

A potent convulsant, trimethylolpropane phosphate (TMPP), was evaluated for long-term effects on measures of social behaviors and anxiety in Long-Evans rats. Animals received three to four daily treatments of TMPP (0.1 mg/kg/ml) beginning at age 23 days in Experiment 1 and 73 days in Experiment 2. Gregariousness was measured in juvenile play and adult social investigation. Anxiousness was measured in the open field and elevated plus-maze. Long-lasting changes in social behaviors were found: play and social investigation were elevated, especially in female rats. Also, an aversive environmental experience associated with TMPP treatment influenced the drug effect on social investigation for males, but not females. In males, TMPP- vs. VEH-treated animals displayed greater social investigation when the treatment was in a positive environment than in an aversive one. In contrast, TMPP- vs. VEH-treated females showed greater social investigation regardless of environmental experience. There were no treatment group differences for measures of anxiety. These results suggest short-term exposure to TMPP may lead to long-lasting changes in specific social behaviors and neural substrates related to them, but not to changes in anxiousness.