POTENTIAL ANIMAL-MODEL OF MULTIPLE CHEMICAL-SENSITIVITY WITH CHOLINERGIC SUPERSENSITIVITY

Multiple Chemical Sensitivity (MCS) is a clinical phenomenon in which individuals, after acute or intermittent exposure to one or more chemi cals, commonly organophosphate pesticides (OPs), become overly sensiti ve to a wide variety of chemically-unrelated compounds, which can incl ude ethanol, caffeine and other psychotropic drugs. The Flinders Sensi tive Line (FSL) rats were selectively bred to be more sensitive to the OP diisopropylfluorophosphate (DFP) compared to their control counter parts, the Flinders Resistant Line (FRL) rats. The present paper will summarize evidence which indicates that the FSL rats exhibit certain s imilarities to individuals with MCS. In addition to their greater sens itivity to DFP, the FSL rats are more sensitive to nicotine and the mu scarinic agonists arecoline and oxotremorine, suggesting that the numb er of cholinergic receptors may be increased, a conclusion now support ed by biochemical evidence, The FSL rats have also been found to exhib it enhanced responses to a variety of other drugs, including the serot onin agonists m-chlorophenylpiperazine and 8-OH-DPAT, the dopamine ant agonist raclopride, the benzodiazepine diazepam, and ethanol. MCS pati ents report enhanced responses to many of these drugs, indicating some parallels between FSL rats and MCS patients, The FSL rats also exhibi t reduced activity and appetite and increased REM sleep relative to th eir FRL controls. Because these behavioral features and the enhanced c holinergic responses are also observed in human depressives, the FSL r ats have been proposed as a genetic animal model of depression. It has also been reported that MCS patients have a greater incidence of depr ession, both before and after onset of their chemical sensitivities, s o cholinergic supersensitivity may be a state predisposing individuals to depressive disorders and/or MCS. Further exploration of the common alties and differences between MCS patients, human depressives, and FS L rats will help to elucidate the mechanisms underlying MCS and could lead to diagnostic approaches and treatments beneficial to MCS patient s.