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R Ader

Publications and source records attributed to R Ader.

At least 55 records · Page 3Linked to original sources
PubMed1987

Behaviorally conditioned enhancement of delayed-type hypersensitivity in the mouse.

Cyclophosphamide (CY), previously used to condition suppression of a number of different immune responses, was used to condition an enhancement of a delayed-type hypersensitivity (DTH) response in mice. Three weeks before sensitization with sheep red blood cells (SRBC), mice were conditioned by pairing their consumption of a saccharin solution (SAC) with injection of CY. Two, three, and four days after sensitization (Day 0), animals were reexposed to SAC and, on Day +3, they were injected with a low dose of CY. This dose suppressed the DTH response to a challenge with SRBC on Day +4 in both conditioned and control animals. Following rechallenge with SRBC on Days +11 and +18, however, DTH responses were enhanced. Conditioned mice that had been reexposed to SAC showed a significantly greater enhancement than either nonconditioned animals or conditioned mice that were not reexposed to SAC. Thus, enhancement as well as suppression of immune responses can be conditioned with CY.

Animals↗
PubMed1987

Taste aversion learning in autoimmune Mrl-lpr/lpr and Mrl +/+ mice.

Conditioned taste aversion to a neutral stimulus paired with an immunosuppressive drug (cyclophosphamide) was assessed in lupus-prone MRL-lpr/lpr and congenic control (MRL +/+) mice. The presence of lymphoproliferation in MRL-lpr/lpr mice was associated with poorer taste aversion learning and varied as a function of the dose of cyclophosphamide. There were no differences in learning performance between MRL-lpr/lpr and MRL +/+ mice when the animals were tested at an age prior to the development of lymphadenopathy, or when lithium chloride or electric shock were used as unconditioned stimuli. These results are consistent with the hypothesis that the immune status of an organism has an impact on behavior and the possibility that behavior can serve an in vivo immunoregulatory function.

Animals↗
PubMed1986

Long-lasting enhancement of the delayed-type hypersensitivity response to heterologous erythrocytes in mice after a single injection of cyclophosphamide.

Previous reports have indicated that cyclophosphamide (CY) treatment can enhance delayed-type hypersensitivity (DTH) reactions by abrogating suppressor T cell functions. Such findings have suggested that cells in the suppressor lineage may be particularly sensitive to this alkylating agent. The experiments reported here demonstrate that a single injection of CY before sensitization can induce a long-lasting state of enhanced DTH responsiveness to sheep red blood cells (SRBC) in mice. This enhancement required concurrent antigenic stimulation and appeared to be antigen-specific. Additionally, CY treatment of sensitized mice before the first antigenic challenge for DTH resulted in suppressed responses to that challenge, followed by enhanced DTH to subsequent challenge with the same antigen. The suppressed response was achieved with a lower dose of CY than the subsequent enhancement and also required concurrent antigenic stimulation. These results indicate that the effects of CY on both effector and suppressor mechanisms are critically dependent upon antigenic stimulation, and suggest that apparent suppressor sensitivity to CY may be a function of differential ability to recover from CY treatment in a context of antigenic stimulation.

Animals↗
PubMed1984

Acquisition and extinction of conditioned suppression of a graft-vs-host response in the rat.

Injection of rats with cyclophosphamide (CY) after their consumption of a novel saccharin-flavored drinking solution results in a conditioned aversion to saccharin and a conditioned suppression of immune responses. In this study, female Lewis X Brown Norwegian F1 rats were conditioned by pairing saccharin with 50 mg/kg CY. Seven weeks later (day 0), a graft-vs-host response (GvHR) was induced in these animals by injecting splenic leukocytes from Lewis donors into a rear footpad. At this time, some conditioned animals were reexposed to saccharin, the conditioned stimulus. During the 7-wk interval between conditioning and immunization, subgroups of conditioned rats were given 0, 4, 9, or 18 extinction trials (saccharin followed by saline injections). Animals receiving 4, 9, or 18 extinction trials showed a greater preference for saccharin on day 0 than did animals receiving no extinction trials, but these groups did not differ among themselves; all conditioned groups showed a lower preference for saccharin than placebo-treated animals. There was a clear effect of number of extinction trials on the GvHR. Animals receiving 9 or 18 extinction trials did not differ from controls, whereas animals receiving 0 or 4 trials had a milder GvHR than did conditioned rats that were not reexposed to saccharin at the time of immunization. These results confirm a previous report of conditioned suppression of a GvHR, demonstrate that conditioned immunopharmacologic responses are subject to experimental extinction, and indicate that conditioned immunosuppression can be dissociated from conditioned taste aversion.

Animals↗
PubMed1982

Behaviorally conditioned immunosuppression and murine systemic lupus erythematosus.

Development of autoimmune disease in female New Zealand hybrid mice was dramatically modified by classical conditioning of immunosuppression. Groups of animals received each week a solution of sodium saccharin (conditioned stimulus). One group of conditioned animals received an injection of cyclophosphamide (the unconditioned stimulus) after half of the weekly occasions when they received the saccharin solution. The rate of development of proteinuria and mortality were significantly retarded in these conditioned mice relative to untreated controls and nonconditioned animals that received unpaired treatment with saccharin and cyclophosphamide.

Conditioning, Psychological↗
PubMed1982

Conditioned suppression of humoral immunity in the rat.

Rats were conditioned by pairing consumption of a novel sodium saccharin drinking solution with the effects of an ip injection of 75 mg/kg cyclophosphamide, an immunosuppressive drug. Five and ten days after conditioning, an experimental group of conditioned animals (Group CS) was reexposed to the saccharin drinking solution. Control animals (Group CSo) were conditioned but were not reexposed to saccharin. On Day 10, 15, or 25 after conditioning, animals were injected ip with sheep erythrocytes (SRBC), and independent subgroups were sampled for hemagglutinating antibody titer 4, 6, or 8 days later. There was a significant effect of sample time (antibody titers 4 days after immunization were lower than values observed 6 and 8 days after immunization) and a significant effect of treatment; conditioned animals reexposed to the CS had an attenuated antibody response. There were no significant differences between Group CSo and a group of placebo-treated animals, but conditioned animals reexposed to the CS had lower antibody titers than placebo-treated animals 4, 6, and 8 days after antigenic stimulation. These differences are more pervasive than those previously reported and suggest that reexposure to a CS may have long-lasting effects. More generally, these data provide further documentation of conditioned immunopharmacologic effects and the impact of behavioral factors in modifying immunologic reactivity.

Animals↗
PubMed1982

Behaviorally conditioned suppression of a graft-versus-host response.

Cyclophosphamide (CY), previously used to condition suppression of humoral immune responses, was used to condition suppression of a graft-versus-host response (GvHR). Female (Lewis x Brown Norway) F1 rats were conditioned by pairing consumption of a saccharin solution with an intraperitoneal injection of CY at 50 mg/kg of body weight 48 days before immunization. On day 0, all animals were injected with a suspension of splenic leukocytes (2 x 10(7) cells per footpad) obtained from female Lewis donors. The regional GvHR was assessed on day 5 by weighing popliteal nodes. Conditioned animals given a single low-dose injection of CY and reexposed to conditioned stimuli had lymph node weights significantly lower than control groups and did not differ from animals given three injections of CY during the ongoing GvHR. The results suggest that conditioned immunosuppression, previously demonstrated in thymus-dependent and thymus-independent humoral immune responses, also affects the popliteal GvHR, a cellular immune response.

Animals↗