Nuclear factor-kappa-B inhibitor modulates the development of opioid dependence in a mouse model of naloxone-induced opioid withdrawal syndrome.
The present study was designed to investigate the effect of diethyl dithiocarbamic acid sodium salt trihydrate (DDA), a selective inhibitor of nuclear factor-kappa-B, on the development of morphine dependence in a mouse model of naloxone-induced opioid withdrawal syndrome. Morphine (5 mg/kg, intraperitoneally) was administered twice daily for a period of 5 days, after which a single injection of naloxone (8 mg/kg, intraperitoneally) precipitated an opioid withdrawal syndrome in mice. Behavioral observations were made for a period of 30 min immediately after naloxone treatment. Withdrawal syndrome was quantitatively assessed in terms of withdrawal severity score and the frequency of jumping, rearing, forepaw licking, and circling. DDA markedly and dose-dependently (P<0.01) attenuated the morphine-naloxone-induced experimental opioid withdrawal syndrome. However, DDA administration did not alter locomotor activity, thus ruling out any sedative action of DDA per se. Further, DDA pretreatment did not alter the acute analgesic effect of morphine. The results suggest that nuclear factor-kappa-B is involved in the development of opioid dependence and the precipitation of its withdrawal syndrome, and thus, may serve as a viable pharmacological target to tackle the problem of opioid addiction.
Rehni
Ashish K
AK
Chitkara College of Pharmacy, Chandigarh-Patiala National Highway, Rajpura, Punjab, India. ashishkrehni@gmail.com
Bhateja
Pradeep
P
Singh
Thakur Gurjit
TG
Singh
Nirmal
N
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004050:Ditiocarb / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D009021:Morphine Dependence; D009043:Motor Activity / Q000187:drug effects; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009293:Opioid-Related Disorders / Q000378:metabolism*; D012720:Severity of Illness Index; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
D000701:Analgesics, Opioid; D016328:NF-kappa B; D009292:Narcotic Antagonists; D009270:Naloxone; D009020:Morphine; D004050:Ditiocarb