Title: Effect of reduced immunity on murine behviors

Author's name: Jose Vidal

Affiliation: University of Barcelona School of Psychology, Barcelona, Spain.

Summary.- Reduction of immunity in mice of the CD1 strain, by administration of methotrexate, did not alter some reliable behaviors in the open-field (ambulation, rearing, defecation). Therefore, moderate depression of immunity may not affect characteristic behaviors.

One issue in psychoneuroimmunology is whether alterations of immunity, increases or decreases, affect behavior. To the author’s knowledge, the effect of immunodepression on behavior has been scarcely investigated (Barnard et al., 1997) and, therefore, this communication reports some preliminary findings on that issue. Reduction of immunity has been achieved by administration of methotrexate, a drug used for treatment of cancer and some autoimmune diseases (Winkelstein, 1994). The behavioral test used was the open-field test, a well characterized test for rodents (Simmel & Bagwell, 1983), and those behaviors reported to be reliable were chosen (ambulation, rearing, and defecation; Gomá & Tobeña, 1978).

A group of 11 male mice, of the CD1 strain, received intraperitoneal (ip.) injections of methotrexate (30 or 50 mg/kg), every 3 or 4 days, during one month (Baggott et al., 1992); another group of 10 mice, of the same sex, age, and strain, received ip. injections of saline. Before the course of methotrexate (baseline), all the mice were assessed behaviorally in the open-field, and immunologically by ip. injection of bovine serum albumin. During treatment (methotrexate or saline), the mice were immunized ip. with rat erythrocytes (3x106 /mouse), to check that the mice were immunodepressed, and thereafter took the open-field test.

Measurements at baseline showed that both groups of mice were of comparable immunity (similar antibody responses to bovine serum albumin; Figure 1) and behavior (similar scores in ambulation, rearing, and defecation; only rearing is reported here, Figure 1). Methotrexate lowered immunity, because mice thus treated produced less antibodies to rat erythrocytes (Figure 1; analysis of covariance [covariate: measurement at baseline]: effect of treatment: F (1,17) = 5.90, p=0.026). Yet, methotrexate did not alter significantly ambulation, defecation (not shown), and rearing (Figure 1; analysis of covariance [covariate: measurement at baseline]: effect of treatment: F (1,18) = 1.06, p=0.31).

Although this preliminary report suggests that decrease of immunity may not affect reliable behaviors in the mouse, some methodological details should be refined before that conclusion can be borne out (e.g., dose and protocol of immunodepressive drug to minimize side effects, type of immunity, cellular or humoral, etc.).

The author acknowledges a fellowship (PB95-0458) from the Spanish Ministry of Education.

References

Baggott, J.E., Morgan, S.L., Freeberg, L.E., Hudson, B.B., Vaugh, W.H., Nair, M.G., Krumdieck, C.L., Koopman, W.J., Gay, R.E., & Gay, S. (1992). Long-term treatment of the MRL/lpr mouse with methotrexate and 10-deazaaminopterin. Agents and Actions , 35 , 104-111.

Barnard, C.J., Behnke, J.M., Gage, A.R., Brown, H., & Smithurst, P.R. (1997). Modulation of behaviour and testosterone concentration in immunodepressed male laboratory mice (Mus musculus). Physiology & Behavior, 61, 907-917.

Gomá, M. & Tobeña, A. (1978). Reliability of various measures obtained in open-field test. Psychological Reports, 43, 1123-1128.

Simmel, E.C. & Bagwell, M. (1983). Genetics of exploratory behavior and activity. In J.L. Fuller and E.C. Simmel (Eds.) Behavior genetics: Principles and applications (pp. 85-115). Hillsdale, New Jersey: Erlbaum.

Winkelstein, A. (1994). Immunosuppressive therapy. In D.P. Stites, A. I. Terr, & T.G. Parslow (Eds.) Basic and clinical immunology (8 th edition, pp. 765-780). London: Prentice Hall.

Figure caption

Figure 1: Immunodepression and behavior.

 and error bars (mean and standard error of mean): saline-injected mice (N=10); * and error bars (mean and standard error of mean): methotrexate-injected mice (N=11). Each arrow indicates one injection of methotrexate (on days 34, 38, and 41, the dose was 30 mg/kg; on days 45, 48, 52, 55, and 59, the dose was 50 mg/kg).