Program in Neuroscience, Washington State University, Pullman, Washington 99164, USA
Chemical intolerance is a phenomenon observed in multiple chemical
sensitivity (MCS) syndrome, an ill-defined disorder in humans
attributed to exposure to volatile organic compounds. Amplification
of symptoms in individuals with MCS resembles the phenomenon
of psychostimulant- and stress-induced sensitization in rodents.
We have recently tested in rats the hypothesis that repeated
chemical exposure produces sensitization of central nervous
system (CNS) circuitry. A rat model of MCS in our laboratory
has employed several endpoints of CNS function after repeated
formaldehyde (Form) exposure (1 h/day
x 5 days/week
x 4 weeks).
Repeated Form exposure produced behavioral sensitization to
later cocaine injection, suggesting altered dopaminergic sensitivity
in mesolimbic pathways. Rats given repeated Form also demonstrated
increased fear conditioning to odor paired with footshock, implicating
amplification of neural circuitry guiding fear responding to
a conditioned odor cue. Recent studies examining the effects
of repeated Form on locomotor activity during each daily exposure
showed a decrease in rearing activity after 12-15 days of Form
exposure compared to air-exposed controls. EEG recordings taken
1 week after withdrawal from daily Form revealed altered sleep
architecture. Some of the differences in sleep disappeared after
subsequent brief (15 min) challenge with Form the next day.
Overall, the findings indicate that repeated low-level chemical
exposure produces behavioral changes that may be akin to those
observed in individuals with MCS, such as greater sensitivity
to chemicals manifest as increased anxiety upon chemical exposure
and altered sleep and/or fatigue. Study of the underlying CNS
changes will provide a basis for mechanistically based animal
models for MCS.
