Behavioral sensitization following exposure to low doses of trimethylolpropane phosphate

Behavioral sensitization is commonly studied within the context of drugs kn own to directly increase activity in the brain's dopamine system, particula rly drugs of abuse. However, the present research suggests such behavioral changes can also be observed following exposure to other compounds that ind irectly affect the dopamine system. One such compound is trimethylolpropane phosphate (TMPP), a bridged organophosphate that can be produced by the pa rtial pyrolysis of certain synthetic lubricants used on military ships and aircraft. Although TMPP is a potent convulsant, it has been demonstrated th at treatment with doses below seizure threshold results in long-term behavi oral sensitization. The effect has been demonstrated with a number of neuro behavioral endpoints, particularly those assessing appetitive responding. M ore specifically, sensitization has been observed in acquisition of schedul e-induced polydipsia (SIP), appetitive reinforcer approach sensitization (A RAS) and social interaction as measured in neonatal ultrasonic vocalization s, juvenile play and adult conspecific approach. Overall, the rats demonstr ated a heightened appetitive response pattern. More specifically, TMPP reli ably reduced the number of SIP sessions necessary to induce asymptotic drin king level and increased the time spent investigating (sniffing) a food rei nforcer as measured in the ARAS task. Specific effects of TMPP on social in teraction 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 eme rged for the measures of adult social investigation where the drug effect w as modulated by such factors as sex and neutral vs. stress-inducing experie nces 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 held exploration. These results suggest that TMPP produces neuroph ysiological changes that persist much longer than the pharmacological effec t of the compound, particularly in the neural correlates for appetitive beh avior. (C) 2001 Elsevier Science B.V. All rights reserved.