Robert Ader

Behaviorally Conditioned Immunosuppression

&NA; An illness‐induced taste aversion was conditioned in rats by pairing saccharin with cyclophosphamide, an immunosuppressive agent. Three days after conditioning, all animals were injected with sheep erythrocytes. Hemagglutinating antibody titers measured 6 days after antigen administration were high in placebo‐treated rats. High titers were also observed in nonconditioned animals and in conditioned animals that were nor subsequently exposed to saccharin. No agglutinating antibody was detected in conditioned animals treated with cyclophosphamide at the time of antigen administration. Conditioned animals exposed to saccharin at the time of or following the injection of antigen were significantly immunosuppressed. An illness‐induced taste aversion was also conditioned using LiCl, a nonimmunosuppressive agent. In this instance, however, there was no attenuation of hemagglutinating antibody titers in response to injection with antigen.

Retention of a passive avoidance response as a function of the intensity and duration of electric shock

Upon leaving an elevated runway to enter a darkened chamber, different groups of rats were given a single electric shock of 0.125, 0.250, or 0.500 mA for 1, 3, or 9 sec. Retention trials, during which latency to enter the darkened chamber and defecation were recorded, were given immediately (30 sec) or 3, 24, or 48 h after the shock trial. Latency and defecation were directly related to both the intensity and duration of the electric shock. No interaction between shock intensity and duration was observed. Response latency was inversely related to the retention interval and, although there was more defecation during the 3-h than during the immediate retention test, this could be interpreted as a recency effect rather than as the incubation of fear.

Continuous recording of maternal behaviour in Rattus norvegicus

Summary It was assumed that the time a lactating rat spends with its litter can be taken as a reflection of maternal behaviour. This was measured continuously in a dual-chambered apparatus which permitted the female to be with or away from its litter for any amount of time at any time of the day. It was found that the total time and the duration of each period that the mother spends with its litter shows an orderly decrease over the 21 days post-partum. Further analyses of these data indicated that there is a 24-hr rhythm in maternal behaviour. The rhythm appears to be inversely related to and may be a direct reflection of the rats characteristic 24-hr activity cycle. A comparison of the time spent with the litter with data obtained from a modified version of Seitzs maternal-behaviour scale yielded similar changes over time for those tests of the scale which did not involve any disruption of the ongoing behaviour of the mother or litter. Otherwise, there was no consistent relationship between these two measures or within the scale itself. Administration of the maternal-behaviour scale to females rearing litters in a single cage indicated that the above findings could be attributed to the use of the dual-chambered apparatus. These data further suggested that some aspects of the maternal-behaviour scale may be artifacts of the conditions of housing or method of administration, and may reflect emotional reactivity rather than maternal behaviour, per se. The continuous recording of maternal behaviour was also found to differentiate between females rearing large and small litters. The time spent with the litter over the 21-day post-partum period decreased more rapidly in females rearing litters of twelve than in females rearing litters of four animals. The data are interpreted as support for the assumption that the time that a lactating rat spends with its litter can be taken as a reflection of maternal behaviour. The main advantages of this procedure are that it provides a continuous recording that is not subject to sampling error or experimenter bias, and it takes advantage of the ongoing mother-litter interactions which are initiated by the animals themselves rather than forced by the proximity of a single cage or by the intervention of an experimenter.

CNS–immune system interactions: Conditioning phenomena

Converging data from different disciplines indicate that central nervous system processes are capable of influencing immune responses. This paper concentrates on recent studies documenting behaviorally conditioned suppression and enhancement of immunity. Exposing rats or mice to a conditioned stimulus previously paired with an immunomodulating agent results in alterations in humoral and cell-mediated immune responses to antigenic stimuli, and unreinforced reexposures to the conditioned stimuli result in extinction of the conditioned response. Although the magnitude of such conditioning effects has not been large, the phenomenon has been independently verified under a variety of experimental conditions. The biological impact of conditioned alterations in immune function is illustrated by studies in which conditioning operations were applied in the pharmacotherapy of autoimmune disease in New Zealand mice. In conditioned animals, substituting conditioned stimuli for active drugs delays the onset of autoimmune disease relative to nonconditioned animals using a dose of immunosuppressive drug that, by itself, is ineffective in modifying the progression of disease. The hypothesis that such conditioning effects are mediated by elevations in adrenocortical steroid levels receives no support from available data. Despite its capacity for self-regulation, it appears that the immune system is integrated with other psychophysiological processes and subject to modulation by the brain.

Effects of lysine vasopressin on passive avoidance learning

On a single conditioning trial, a 1-sec electric shock (.125 or.250 mA) was administered when rats entered a darkened chamber from a lighted elevated runway. Latency to enter the chamber was recorded on retention trials given 24 and 48 h later. Animals received subcutaneous injections of varying doses of lysine vasopressin or a placebo solution immediately after the training trial or immediately before the first retention trial. Nonshocked control animals showed no increase in response latencies on successive trials, nor was there a difference between the placebo and vasopressin groups under the “no-shock” condition. Treatment with lysine vasopressin increased resistance to extinction, irrespective of the time of treatment.

Effects of vasopressin on active and passive avoidance behavior.

Male rats were trained in an active avoidance and/or a “step-through” type of passive avoidance situation. Lysine vasopressin administration resulted in resistance to extinction of active avoidance behavior if it was injected 1 hr prior to the third and final acquisition session; peptide treatment 6 hr prior to this session did not affect extinction. Resistance to extinction of passive avoidance behavior was also obtained when lysine vasopressin was injected 1 hr prior to the first retention trial on Day 3 of training. Peptide administration 6 hr prior to this trial appeared to be ineffective. If rats were trained in both the active and passive avoidance situation spaced 6 hr apart, lysine vasopressin only affected extinction of the particular behavior tested 1 hr after the single administration of peptide. The behavioral effects of lysine vasopressin evidently depend upon the time of treatment. No evidence of generalization was observed even though both behavioral responses were aversively motivated.

Effects of early experience on adrenocortical reactivity

Abstract Unmanipulated control animals and rats that were exposed to handling or electric shock either pre- or post-weaning were subsequently stimulated by being placed into a novel environment for 5 sec or 3 min. Plasma corticosterone levels were sampled 5, 15, or 30 min following the cessation of this stimulation and in animals that received no such stimulation. The handled and shocked animals did not differ. As a group, however, the corticosterone response of the manipulated animals showed them to be less reactive than controls irrespective of the duration of stimulation.

Plasma Corticosterone Response to Parameters of Electric Shock Stimulation in the Rat

&NA; Rats were subjected to one of six intensities of electric shock administered for 30, 60, 120, or 240 sec., and then sacrificed immediately or 5, 15, or 60 min. later. Plasma corticosterone levels were determined and compared to values obtained from both unmanipulated controls and “handled” rats. It was found that merely placing the animals in the experimental cage increased corticosterone levels, and these levels were further elevated as shock intensity and duration were increased.

Presidential address--1980. Psychosomatic and psychoimmunologic research.

Much of what I have to say, I have said before. As a matter of fact, much of what I have to say many of you have said before. I have been persuaded, however, that it bears repeating. WhiJe I am talking to you, I am really addressing my remarks to those who are not here; those who are not committed t

Effects of prenatal maternal handling and differential housing on offspring emotionality, plasma corticosterone levels, and susceptibility to gastric erosions.

&NA; Offspring of rats that were either unmanipulated or handled throughout pregnancy were fostered to unmanipulated females at birth and group‐housed at weaning. Behavioral responses to a reaction‐to‐handling test indicated that prenatally stimulated animals were somewhat less emotional than controls. Also, there was an attenuated plasma corticosterone response to this test in the prenatally handled females. Among females, prenatally manipulated animals were more susceptible to immobilization‐produced gastric erosions. In a second experiment, prenatally handled and control rats, reared by unmanipulated females, were housed by groups or individually at weaning. The basic findings of Experiment 1 were confirmed and an interaction between prenatal treatment and housing was observed, the difference between prenatally handled and control animals being most pronounced among the individually housed populations.