BICUCULLINE ENHANCES THE CORTICOSTERONE SECRETION INDUCED BY LIPOPOLYSACCHARIDE AND INTERLEUKIN-1-ALPHA IN MALE-RATS

Lipopolysaccharide (LPS)-induced inflammatory stress activates the hyp othalamus-pituitary-adrenal (HPA) function, Interleukin-1 (IL-1) is on e of the key factors during this event; however, the mechanisms mediat ing IL-1 stimulation of HPA axis are still unclear, The present study evaluated the possible involvement of gamma-aminobutyric acid (GABA) i n LPS-induced activation of HPA axis in adult male rats, In addition, the possible existence of diurnal changes of LPS-induced HPA axis acti vity was also investigated. Bicuculline (0.8 mg/kg BW), a GABA-A recep tor antagonist and GABA (1 g/kg BW) were intraperitoneally (ip) inject ed 15 min before LPS (2 mg/kg BW, ip) or recombinant human IL-1 alpha (mu g/rat) administration in intact rats, Control animals received an equivalent volume of 0.9% saline. Rats were sacrificed at 60 min or 90 min after LPS, or IL-1 alpha or saline injection, Plasma corticostero ne levels were measured by radioimmunoassay, Results showed that pretr eatment with bicuculline enhanced both LPS- and IL-1-induced corticost erone secretion; while pretreatment with GABA significantly reduced th e LPS-stimulated corticosterone release (p<0.05, vs LPS alone), The ef fect is dependent on the time of sampling and such effect of bicuculli ne or GABA was not observed when rats were stimulated in the evening, In addition, the maximal changes of plasma corticosterone following LP S administration in the evening were significantly lower than in the m orning (p<0.01). The present study provides evidence that GABA is invo lved, at least in part, in the neuroendocrine regulation of LPS/interl eukin-1a-induced corticosterone secretion via GABA-A receptor in rats, In addition, the response of plasma corticosterone to LPS has a diurn al variation, which corresponds to a diurnal change of GABAergic modul ation of the immunoneuroendocrine response.