Potential animal model of multiple chemical sensitivity with cholinergic supersensitivity

Abstract

Multiple Chemical Sensitivity (MCS) is a clinical phenomenon in which individuals, after acute or intermittent exposure to one or more chemicals, commonly organophosphate pesticides (OPs), become overly sensitive to a wide variety of chemically-unrelated compounds, which can include ethanol, caffeine and other psychotropic drugs. The Flinders Sensitive Line (FSL) rats were selectively bred to be more sensitive to the OP diisopropylfluorophosphate (DFP) compared to their control counterparts, the Flinders Resistant Line (FRL) rats. The present paper will summarize evidence which indicates that the FSL rats exhibit certain similarities to individuals with MCS. In addition to their greater sensitivity to DFP, the FSL rats are more sensitive to nicotine and the muscarinic agonists arecoline and oxotremorine, suggesting that the number of cholinergic receptors may be increased, a conclusion now supported by biochemical evidence. The FSL rats have also been found to exhibit enhanced responses to a variety of other drugs, including the serotonin agonists m-chlorophenylpiperazine and 8-OH-DPAT, the dopamine antagonist raclopride, the benzodiazepine diazepam, and ethanol. MCS patients report enhanced responses to many of these drugs, indicating some parallels between FSL rats and MCS patients. The FSL rats also exhibit reduced activity and appetite and increased REM sleep relative to their FRL controls. Because these behavioral features and the enhanced cholinergic responses are also observed in human depressives, the FSL rats have been proposed as a genetic animal model of depression. It has also been reported that MCS patients have a greater incidence of depression, both before and after onset of their chemical sensitivities, so cholinergic supersensitivity may be a state predisposing individuals to depressive disorders and/or MCS. Further exploration of the commonalties and differences between MCS patients, human depressives, and FSL rats will help to elucidate the mechanisms underlying MCS and could lead to diagnostic approaches and treatments beneficial to MCS patients.