BEHAVIORAL-EFFECTS OF LIPOPOLYSACCHARIDE IN RATS - INVOLVEMENT OF ENDOGENOUS OPIOIDS

Activation of the immune system in response to either infection or lip opolysaccharide (LPS) produces neurophysiological, neuroendocrine and behavioral changes. Some of the physiological consequences of LPS are mediated by endogenous opioid peptides. The following studies were des igned to characterize the effects of LPS in several behavioral paradig ms, and to determine the role of opioids in mediating these effects. T he effects of LPS on locomotor and self-care activity were assessed in the open field test. Rats were injected with either saline or a dose of LPS (25, 50, 100, or 1000 mu g/kg). 4 h later, the animals were pla ced in an open field and the numbers of line crossings, rearings and g rooming episodes were counted. LPS significantly suppressed the three open field behaviors in a dose-related manner. The effect of LPS on se nsitivity to pain was determined using the hot-plate and tail-flick te sts. Administration of LPS (200 mu g/kg) increased pain sensitivity in the hot plate test 30 min after drug administration, but produced a s ignificant analgesic response 4 h after drug administration in both te sts. Further characterization of LPS-induced analgesia demonstrated th at it began about 2 h after and disappeared 30 h after the administrat ion of LPS. Administration of naltrexone completely blocked the analge sic effects of LPS 4 h after its administration, but had no effect on LPS-induced suppression of activity in the open field. The effect of L PS on body temperature was biphasic, producing hypothermia at 2 h and hyperthermia at 8-30 h after its administration. Naltrexone had no eff ect on the body temperature changes induced by LPS. These results sugg est that endogenous opioids mediate the analgesic effects of LPS, but they are involved neither in mediating LPS-induced suppression of loco motor and self care behaviors nor in alterations of body temperature.