Hemorrhagic shock is shown to disturb the behavior of rats in the open field test. Infusion of a mixture of thyrotropin releasing hormone and FMRFa (Phe-Met-Arg-Phe amide) in subthreshold doses led to a partial recovery of the neurological status.
Key Words: hemorrhagic shock; thyrotropin releasing hormone; FMRFa; naloxone; neurological statusAdministration of opioid antagonists such as naloxone is one way to correct hemorrhagic shock [7], However, some claim that naloxone is ineffective and even exerts negative effects in hemorrhagic shock [2,6]. Hence, we decided to investigate the mode of action of endogenous antiopioids.Previously we showed that some peptides (thyrotropin releasing hormone -TRH and Phe-MetArg-Phe amide -FMRFa) suppressing the effects of opioids can exert a pronounced protective effect on the cardio-and hemodynamics in narcotized and awake rats with hemorrhagic shock, although in many cases it is associated with side effects. Therefore, we attempted to investigate the effects of these peptides as components of mixtures with their doses reduced to subthreshold. Simultaneous intraarterial infusion of FMRFa and TRH in subthreshold doses (0.01 mg/kg/min) improved the recovery of arterial pressure after hemorrhagic shock.It is especially interesting to analyze the effects of such a mixture on the behavioral reactions in the posthemorrhagic period, when persistent changes develop in the metabolic and ultrastructural charac- teristics of biosynthetic processes in the brain [8]. Hence, we analyzed the aftereffect of this peptide mixture on the neurological status.
MATERIALS AND METHODSHemorrhagic shock was induced in awake rats (outbred females) by letting 40% of the blood through a catheter implanted in the carotid artery under Nembutal (40 mg/kg) narcosis. Immediately after bloodletting, a 40-rain intraarterial infusion of a mixture of FMRFa and TRH (Sigma) in subthreshold doses (0.01 mg/kg/min) was started. Equivalent volumes of normal saline were infused to control animals.The orienting-exploratory activity and emotional status of the animals were assessed on days 2, 4, and 7 after blood loss in the open field test (a stress-free modification) [5]. Horizontal motor activity (HMA), vertical activity, grooming movements, and the number of radial transpositions into the center of the field were visually recorded for 2 min.For additional control, in order to single out the effects of the operation and hemorrhagic shock on behavior, two groups of animals were examined: intact and sham-hemorrhagic. An operation without bloodletting was performed in sham-hemorrhagic rats.