SOCIAL CONFRONTATION AND TUMOR-METASTASIS IN RATS - DEFEAT AND BETA-ADRENERGIC MECHANISMS

The effect of social confrontation on the susceptibility to metastatic development was studied in rats. An intruder male Fischer 344 (F344) was introduced to a male-female Long-Evans pair and the behavior was r ecorded during the first 30 min of a 7-h confrontation session. Mammar y tumor cells (MADB106), syngeneic to the inbred F344 rat, were inject ed IV to the intruder 1 h after the beginning of the confrontation ses sion, and the lung retention of tumor cells was determined 24 h later. In this tumor model, metastases develop only in the lungs. Retention of tumor cells and the consequent development of lung colonies are kno wn to be highly controlled by the activity levels of natural killer ce lls during the first 24 h after tumor inoculation but not later. Twent y of the 21 intruders were attacked by resident males and 19 displayed submissive behavior. A significant increase in lung tumor retention w as evident in intruders compared to both control groups: home cage and new environment. The magnitude of this increase was higher in intrude rs that frequently displayed submissive behavior (indicating social de feat). Pretreatment with the beta-adrenergic antagonist, butoxamine, r educed the effects of social confrontation by approximately 50%, and a drenal demedullation almost abolished it without significantly affecti ng the social interaction. These findings suggest that the nature of i ntruder-resident interaction, rather than being subdominant or exposur e to an unfamiliar environment, has a marked influence on the intruder 's susceptibility to metastatic development. These effects of social c onfrontation seem to be mediated by adrenergic mechanisms, possibly vi a adrenergic influence on NK function and distribution.