Behavioral Responses to Cyclophosphamide in Animals With Autoimmune Disease
Robert Ader University of Rochester School of Medicine and Dentistry
Lesioning or electrical stimulation of areas within the hypothalamus influence immune responses (e.g., Stein, Schleifer, & Keller, 1981). More recently, it has been found that activation of the immune system can result in electrophysiological changes within the brain (e.g., Besedovsky, Sorkin, Felix, & Haas, 1977). Similarly, immunologic reactivity is altered by the exogenous administration or the endogenous release of hormones and neurotransmitters for which lymphocytes, monocytes, macrophages, and other cells of the immune system bear receptors (e.g., Weigent & Blalock, 1987), and conversely, the response to immunization is associated with the release of hormones and neurotransmitters (e.g., Besedovsky et al., 1983). Behavioral factors, notably "stress" and Pavlovian conditioning that presumably operate via neuroendocrine changes, are also capable of influencing immune responses ( Ader & Cohen, 1985; Ader & Felten, Cohen 1991). As with the reciprocal relationship between neural and immune processes and between endocrine and immune processes, there are experimental and clinical data to suggest that the immunologic state of the organism has consequences for behavior ( Ader, Grota, Moynihan, & Cohen, 1991; Crnic, 1991; Kurstak, Lipowski, & Morozov, 1987; Schiffer & Hoffman, 1991; Weiner, 1991).
Several behavioral studies have been conducted on strains of mice that spontaneously develop an autoimmune disease that is, in many respects, identical to systemic lupus erythematosus in humans ( Theofilopoulos & Dixon, 1985). The most extensively studied model is the New Zealand hybrid (NZB x NZW)F1 mouse. The more susceptible females develop a lethal glomerulonephritis beginning at about 8 months of age. Another