BEHAVIORAL AND AUTONOMIC RESPONSES TO INTERMITTENT SOCIAL STRESS - DIFFERENTIAL PROTECTION BY CLONIDINE AND METOPROLOL

The present study investigated physiological and pharmacological chara cteristics of socially ''stressed'' animals. Specifically, we examined (1) to what degree autonomic and behavioral ''stress'' reactions duri ng intermittent confrontations between an intruder male adult Long-Eva ns rat with an aggressive resident undergo habituation, and (2) to wha t extent the defeat-experienced animal can be protected against these ''stress'' reactions with clonidine or metoprolol, two adrenergic agen ts with clinical anxiolytic effects. We developed an acute social stre ss situation that consisted of initially placing an experimental rat a s an intruder into the homecage of a resident while the resident was n ot present, thereafter permitting brief physical agonistic interaction s with the reintroduced resident until the intruder was forced into a submissive supine posture and emitted ultrasonic vocalizations (USV), and eventually exposing the intruder to the resident's threats for one hour, while being shielded from potentially injurious attacks (''thre at encounter''). Over the course of the initial 4-weekly threat encoun ters the acute tachycardia but not the hyperthermic stress responses d ecreased in magnitude. Following the first three threat encounters cor e temperature (T-c) was significantly elevated for at least 3 h. The T -c was already elevated when the repeatedly defeated intruder was conf ronted with the olfactory cues of the resident's cage. This conditione d ''anticipatory'' hyperthermia developed in the course of the first t hree confrontations and was paralleled by a decrease in exploratory an d motor behavior and by an increase in defensive behaviors and in both types of USV emitted in the ''low'' (20-30 kHz) and the ''high'' (31- 70 kHz) frequency range. Clonidine (0.01-0.1 mg/kg, IP), an alpha(2)-a drenergic agonist and metoprolol, a beta-adrenergic blocker (1.0-10.0 mg/kg, IP), dose-dependently prevented the tachycardic response to str ess. Only clonidine, but not metoprolol, also attenuated the rise in T -c during the 1-h agonistic interaction. Clonidine decreased those aff ects of motor behavior (e.g. rearing, walking) that are of lesser ''co st'' for the individual but maintained high levels of defensive reacti ons and increased the duration of ''low'' USV. The high doses of cloni dine (0.06, 0.1 mg/kg) attenuated the homeostatic regulation and sedat ed the intruder while exposed to threats during a social confrontation . The absence of attenuation of the high level of defensive behavior a nd the prolonged ''low'' USV suggest a stress intensification by the h igher doses of clonidine. In conclusion, after the fourth encounter, t he autonomic, behavioral and vocal response pattern prior to and durin g repeated weekly confrontations show no evidence for habituation for the following 6 weeks. Moreover, adrenergic therapeutic agents that ar e applied to treat symptoms of anxiety block the tachycardic response but may actually intensify defensive behavior and certain ''stress'' v ocalizations.