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The purpose of the present study was to examine the effect of cycloheximide (Cx) - inhibitor of protein synthesis, on the development of pyrogenic tolerance to LPS. It has been observed that Cx at a dose of 1 mg/kg given intravenously 1 h prior to LPS did not prevent fever response, however it modified the induction of pyrogenic tolerance. It was manifested in existence of the second phase of fever after the following administrations of LPS into rabbits pretreated with Cx. In control group of rabbits the induction of pyrogenic tolerance was accompanied with decaying of the second peak of fever visible as early as the second dose of LPS.
The aim of present study was to evaluate mechanisms involved in thermomodulatory effect LPK in rats.Experiments were performed on adult Wistar male rats. LPK was applied either intracerebroventricularly (icv), or intraperitoneally (ip) using the similar program and technique of experiments as in our previous study. We confirmed in this paper the results of our previous reports that icv administration LPK at the dose of 20 nmol induced evident significant rectal hypothermia, while lower dose LPK of 1 nmol icv exerted significant hyperthermic effect. Peripherally applied LPK at the range of doses 10-100 nmol/100 g ip displayed slight bimodal (hyperthermic and hypothermic) effect on rectal temperature. Prior administration of haloperidol, an antagonist of central dopamine receptors blocked both effects LPK applied either icv or ip. Obtained results indicate that both hypothermic and hyperthermic effects LPK are also modulated by central dopaminergic receptors.
The consequences of selective activation of brain somatostatin receptor-2 (sst2) were assessed using the sst2 agonist, des-AA1,4-6,11-13-[DPhe2,Aph7(Cbm),DTrP8]-Cbm-SST-Thr-NH2. Food intake (FI) was monitored in ad libitum fed rats chronically implanted with an intracerebroventricular (i.c.v.) cannula. The sst2 agonist injected i.c.v. at 0.1 and 1 µg/rat dose-dependently increased light phase FI from 2 to 6 hours post injection (2.3±0.5 and 7.5±1.2 respectively vs. vehicle: 0.2±0.2 g/300 g bw, P<0.001). Peptide action was reversed by i.c.v. injection of the sst2 antagonist, des-AA1,4-6,11-13-[pNO2-Phe2,DCys3,Tyr7,DAph(Cbm)8]-SST-2Nal-NH2 and not reproduced by intraperitoneal injection (30 µg/rat). The sst2 antagonist alone i.c.v. significantly decreased the cumulative 14-hours dark phase FI by 29.5%. Other behaviors, namely grooming, drinking and locomotor activity were also increased by the sst2 agonist (1 µg/rat, i.c.v.) as monitored during the 2nd hour post injection while gastric emptying of solid food was unaltered. Rectal temperature rose 1 hour after the sst2 agonist (1 µg/rat, i.c.v.) with a maximal response maintained from 1 to 4 hours post injection. These data show that selective activation of the brain sst2 receptor induces a feeding response in the light phase not associated with changes in gastric emptying. The food intake reduction following sst2 receptor blockade suggests a role of this receptor in the orexigenic drive during the dark phase.
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