Alteration in hypnotic effect of pentobarbital following repeated agonistic confrontations in mice

Abstract

We investigated how repeated agonistic confrontations affect the hypnotic effect of pentobarbital (PB) in male mice, using a resident-intruder paradigm. PB concentrations in the cortex, midbrain and brainstem were determined. Agonistic confrontations were terminated after 10 or 20 attack bites, and were repeated for 5 consecutive days. Immediately after the last encounter, PB (55 mg/kg, IP) was administered to both resident and intruder mice. Compared to the control group, intruders exposed to 20 daily attack bites showed a significant prolongation of the latency to sleep and a shortening of the duration of sleeping time. At the stage of induction, no significant difference in brain PB levels was found between the "defeated" and control intruders. At the stage of recovery, however, the "defeated" intruders showed a significantly low level of PB in all brain areas. In contrast, attacking resident mice did not show any significant changes in either the hypnotic effect or regional brain concentration of PB. Because pretreatment with naloxone prior to daily agonistic confrontation antagonized the alteration in PB-induced hypnosis, it seems that endogenous opioid mechanisms may participate in this phenomenon. The present study indicates that susceptibility to a hypnotic drug can be altered by chronic social conflict experience.