PROPOSED ANIMAL NEUROSENSITIZATION MODEL FOR MULTIPLE CHEMICAL-SENSITIVITY IN STUDIES WITH FORMALIN

A potentially promising line of animal research relevant to multiple c hemical sensitivity (MCS) is that of sensitization in the central nerv ous system (CNS), particularly limbic pathways in the brain. Sensitiza tion is the progressive and enduring enhancement in behavioral and neu rochemical responses that occurs after repeated exposure to psychostim ulants or environmental stressors. Since the onset and progression of sensitization has many parallels with that of MCS, it has been propose d that MCS may be initiated through a mechanism similar to the sensiti zation of CNS components occurring in the rodent. To rest this hypothe sis, female Sprague-Dawley rats were exposed to formalin vapors (FORM, 11 ppm) or water vapor (control) 1 h/day for 7 days. The next day, a saline injection was given followed by a cocaine injection(15 mg/kg, i .p.) 24 h later, and locomotor activity was monitored. Animals pretrea ted with repeated FORM inhalation demonstrated a significantly enhance d locomotor response to cocaine compared to controls, an indicator tha t specific limbic pathways may have been sensitized. At 4 weeks of wit hdrawal from FORM exposure, a subset of animals remained sensitized to a cocaine challenge. No differences were found between groups after a saline injection. In a second experiment, animals were screened prior to FORM or water exposure for their response to a novel situation, a measure believed to reflect an animal's general responsiveness to stim uli. Rats were divided into high responders (HR) or low responders (LR ), based on their locomotion in a novel cage. Results from three behav ioral tests demonstrated that HR and LR were differentially affected b y exposure to FORM. In a passive avoidance test, HR and LR appeared to be different in their distribution of responses, while HR and LR resp onses in the FORM group were nearly identical. On the elevated plus ma ze test of anxiety, HR spent more time on the open arms than LR in bot h treatment groups, with significant differences between HR and LR in the FORM, but not water, treated group. On a hot plate test to measure nociceptive levels, no differences occurred between HR and LR in the control group, whereas nociception of LR tended toward an increase com pared to HR in the FORM-exposed group. Results from the second experim ent suggest that the effects of FORM exposure may be obscured by exami ning behavior in a heterogeneous population (HR and LR). This approach using animal models may help define neural substrates that mediate th e amplification of responses of a subpopulation of individuals to chem icals in the environment.