The immunomodulating effects of specific opioid antagonists after their intracerebroventricular application

Abstract

The role of central opioid receptor types in the modulation of humoral immune response was not investigated so far. Therefore, the aim of the present work was to investigate the possible role of these receptors in immunomodulation. For this purpose, male Wistar rats were intracerebroventricularly (icv) injected with opioid receptor specific antagonists. Control groups of rats were treated icv with physiological saline. Primary humoral immune response was determined by the "plaque-forming cell assay" (PFC response). ICI 174864, a selective d opioid receptor antagonist, administered icv at doses of 0.1; 1; 10; 20 and 50 mg/kg bw caused a statistically significant immunosuppression. b-funaltrexamine (b-FNA), specific m opioid receptor antagonist, applied icv produced a significant immunosuppression only at lower doses of 0.01 and 0.1 mg/kg. Nor-binaltorphimine (nor-BNI), a selective k opioid receptor antagonist administered icv, produced significant immunopotentiation at all applied doses (0.1; 1; 10 and 50 mg/kg bw) except for the lowest dose 0.01 mg/kg bw. Quaternary naltrexone (QNTx), which is a m opioid antagonist at lower doses, but a nonselective opioid antagonist at higher doses, caused statistically significant potentiation on PFC response only when it was given icv at doses of 1 and 10 mg/kg bw. The results indicated differential involvment of central opioid receptor subtypes in immunomodulation.

Uloga samostalno intracerebroventrikularno (icv) primenjenih antagonista opioidnih receptora na humoralni imuni odgovor do danas nije proučavana. Stoga je cilj ovog rada bio da rasvetli efekte ovih supstancija u imunomodulaciji. U tu svrhu koristili smo Vistar pacove, težine 200-250 g, koji su čuvani pod standarnim uslovima. Suptancije su icv aplikovane i sve grupe imale su kontrolne grupe koje su bile tretirane ekvimolarnim fiziološkim rastvorom. Imuni odgovor je odredjivan merenjem broja hemolitičkih plaka (PFC) odgovor. ICI 174864, selektivni delta opioidni antagonist, icv aplikovan u dozama od 0,1;1;10;20 i 50 mg/kg tt prouzrokovao je statistički značajnu imunosupresiju. Beta-funaltreksamin (beta-FNA), specifični mi opioidni antagonist icv aplikovan izazvao je statistički značajnu imunosupresiju, kada je bio primenjen u dozama 0,01 i 0,1 mg/kg tt. Nor-binaltorfimin (nor-BNI), selektivni kapa opioidni antagonist icv primenjen, prouzrokovao je statistički značajnu imunopotencijaciju u svim aplikovanim dozama (0,1; 1; 10 i 50 mg/kg tt), izuzev u najnižoj dozi (0,01 mg/kg tt). Kvaternerni naltrekson (QNTx) koji se ponaša kao mi opioidni antagonist u nižim dozama, a delta opioidni antagonist u višim dozama, ne prelazi krvno moždanu barijeru icv aplikovan izazvao je statistički značajnu potencijaciju PFC odgovora, ali samo kada je primenjen u dozama od 1 i 10 mg/kg tt.