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Chemical intolerance (CI) in humans is a poorly understood phenomenon of uncertain etiology, seemingly influenced by multiple factors both within and between affected individuals. Several authors have suggested that the development of CI in some individuals may be due, at least in part, to Pavlovian conditioning processes in which the expression of overt symptoms to certain substances reflects classically conditioned responses to previously neutral olfactory and contextual stimuli. In this paper, we describe the potential relationship between olfactory and contextual conditioning in experimental animals and the development and expression of CI in humans. Furthermore, as significant advances have been made in delineating the brain areas that underlie these learned responses, we also review recent research on the contributions of the amygdala and perirhinal cortical region to olfactory and contextual fear conditioning.

Idiopathic environmental intolerance (IEI) is a poorly understood condition that may involve disturbances in immunologic, neurologic, endocrine, behavioral, emotional, and cognitive processes. This chapter reviews theories and evidence that behavioral conditioning processes, including pharmacologic sensitization, conditioned immunomodulation, and conditioned odor and taste aversions, may play a role in the development and maintenance of IEI. It also reviews the psychophysiologic concepts of individual response specificity and situational response stereotypy as potential explanations for the individual differences observed in specific responses to environmental stimuli in patients with IEI. Finally, the treatment implications of a conditioning account of IEI are discussed as part of a more comprehensive treatment approach that incorporates other behavioral and nonbehavioral strategies.

Two genes (L5-67 and LUQ-1) that encode neuropeptide precursors have recently been shown to be expressed in a distinct and non-overlapping manner in the five left upper quadrant (LUQ) cells of the abdominal ganglion of Aplysia (Landry et al. [1992]. J. Neurobiol 23:89-101). By using wholemount immunohistochemistry and radioimmunoassay (RIA), the pattern of expression of these two genes was assessed at the protein level throughout the central nervous system (CNS) and in peripheral tissues of Aplysia californica. The distribution of LUQ-1 precursor-like immunoreactivity was fairly limited, occurring in the ventral LUQ cell (L5) and in a total of approximately 20 additional neurons in the abdominal and cerebral ganglia. L5-67 precursor-like immunoreactive material was more prevalent, appearing in a total of approximately 100 neurons distributed among each of the central ganglia. Identified L5-67-immunoreactive neurons included the four dorsal LUQ cells (L2-4 and L6) and two giant neurons (R2 and LPI1). In one group of cells, the H cluster of the cerebral ganglion, L5-67 immunofluorescence was substantially more intense in larger versus smaller animals, suggesting that this peptide precursor is subject to developmental regulation in certain neurons. Immunoelectron microscopic examination of the subcellular localization of L5-67 immunoreactivity in LUQ cell somata and axons revealed its association with dense-core vesicles (approximately 114 nm in diameter). In the periphery, L5-67-immunoreactive fibers were detected in specific regions of the circulatory system (auricle, ventricle, cristae aorta, anterior aorta) and the reproductive system (genital ganglion, large hermaphroditie duct, small hermaphroditie duct, ovotestis). The kidney and the intestine, two tissues in which considerable secretion and absorption occur, contained material immunoreactive to both L5-67 and LUQ-1 antisera. The localization of the two peptide precursors in these tissues differed substantially, with L5-67 occurring in widely ramifying varicose fibers, whereas LUQ-1 was found in restricted foci of fibers and in small spherical cells that appeared to lack processes. These results support previous findings concerning the heterogeneity of neurotransmitter phenotypes in the LUQ cells. Furthermore, they are indicative of a fairly broad role for the L5-67-derived neuropeptides, and a more limited role for the LUQ-1-derived neuropeptides, in the regulation of the visceral organ systems of Aplysia.