Behavioral sensitization following exposure to low doses of trimethylolpropane phosphate

Abstract

Behavioral sensitization is commonly studied within the context of drugs known to directly increase activity in the brain's dopamine system, particularly drugs of abuse. However, the present research suggests such behavioral changes can also be observed following exposure to other compounds that indirectly affect the dopamine system. One such compound is trimethylolpropane phosphate (TMPP), a bridged organophosphate that can be produced by the partial pyrolysis of certain synthetic lubricants used on military ships and aircraft. Although TMPP is a potent convulsant, it has been demonstrated that treatment with doses below seizure threshold results in long-term behavioral sensitization. The effect has been demonstrated with a number of neurobehavioral endpoints, particularly those assessing appetitive responding. More specifically, sensitization has been observed in acquisition of schedule-induced polydipsia (SIP), appetitive reinforcer approach sensitization (ARAS) and social interaction as measured in neonatal ultrasonic vocalizations, juvenile play and adult conspecific approach. Overall, the rats demonstrated a heightened appetitive response pattern. More specifically, TMPP reliably reduced the number of SIP sessions necessary to induce asymptotic drinking level and increased the time spent investigating (sniffing) a food reinforcer as measured in the ARAS task. Specific effects of TMPP on social interaction were an increase in ultrasonic vocalizations when the neonate was isolated from the dam and littermates and an increase in both measures of juvenile play (pins and dorsal contacts). A complex set of interactions emerged for the measures of adult social investigation where the drug effect was modulated by such factors as sex and neutral vs. stress-inducing experiences coincident with the drug treatment. In contrast to the above results, no behavioral changes were recorded for measures in the elevated plus maze and open field exploration. These results suggest that TMPP produces neurophysiological changes that persist much longer than the pharmacological effect of the compound, particularly in the neural correlates for appetitive behavior.