Consistent with the findings of human research suggesting that stress may influence the carcinogenic process, data derived from infrahuman experimentation have revealed that aversive insults may potentiate or inhibit tumorigenicity. The nature of the change, however, is dependent on a number of psychological, experiential, and organismic variables. Exacerbation of tumor growth is evident following acute exposure to uncontrollable, but not controllable, stress. Moreover, the effects of aversive stimuli vary as a function of the organism's prior stress history as well of social housing conditions. The fact that stress influences neurochemical, hormonal, and immunological functioning and that these changes are subject to many of the same manipulations that influenced the carcinogenic process suggests a relation between these three mechanisms and the stress-induced alterations of tumor growth. This contention is supported by the findings that pharmacological manipulations that modify these endogenous substrates have predictable effects on tumorigenesis.

Growth of syngeneic P815 mastocytoma in DBA/2J male mice was evaluated as a result of various stress regimens. A single session of inescapable shock resulted in earlier tumor appearance, exaggeration of tumor size, and decreased survival time in recipient animals. Escapable shock had no such effects. The effects of the inescapable shock were mitigated if mice received long-term shock treatment.

No abstract

Rats were trained to run down a runway for food in the goal box, and were then tested with one trial per day for 5 days. After running in the runway and eating in the goal box each rat was injected with a drug and returned to the empty goal box for 50 min. Over the 5 trials, rats that received morphine sulphate increased their running speed approximately 400% while the amount of food they ate in the goal box decreased to about 70% of baseline values. The running speed of rats that received lithium chloride decreased to about 30%, while the amount of food they ate decreased to less than 10% of baseline. These two variables did not change for rats that received saline injections. The large increases in running speed observed in the rats that received morphine injections were attributed to an interaction (but not simple summation) between the positive reinforcing effects of morphine and food. The accompanying paradoxical decrease in amount eaten was discussed in terms of the complex pharmacological properties of morphine and it was suggested that morphine may have a reinforcing effect on behavior that is independent of its affective properties.

Immediately following exposure to 60 inescapable shocks, Swiss-Webster mice had significantly reduced hypothalamic norepinephrine (NE). Within 24 hr NE levels returned to control values. Reexposure to as few as 10 shocks 24 hr after initial stress exposure resulted in a significant decline of hypothalamic NE. Moreover, at this interval after inescapable shock, escape performance was severely disrupted, with a large proportion of mice exhibiting numerous failures to escape shock. Increasing brain dopamine (DA) and NE by L-dopa treatment prior to inescapable shock prevented the escape deficits. Conversely, pairing five inescapable shocks with NE depletion by FLA-63, or both DA and NE depletion by a-methyl-p-tyrosine, disrupted escape performance 24 hr later. Residual drug effects, state dependence, or sustained amine turnover could not account for the behavioral changes observed. Data are discussed in terms of catecholamine mediation of escape performance through variations in response maintenance abilities. Furthermore, it is suggested that the long-term effects of inescapable shock may be due to sensitization effects or conditioned amine depletion.Exposure to inescapable shock has been shown to disrupt escape performance in a variety of animal species (see reviews in Maier & Seligman, 1976;Weiss, Glazer, & Pohorecky, 1976). The performance deficit is characterized not only by retarded escape latencies but by frequent failures to escape shock as well. In rodents the time course for the interference is dependent upon the shock parameters used during the initial stress session. Following long-duration shock of moderate intensity, a pronounced performance deficit is apparent as long as 1-7 days later; however, only a moderate deficit, if any, is seen at a 30-min interval (Glazer &