title: In vivo and in vitro attenuation of naloxone-precipitated experimental opioid withdrawal syndrome by insulin and selective KATP channel modulator.
abstract: BACKGROUND
  Opiate exposure for longer duration develops state of dependence in humans and animals, which is revealed by signs and symptoms of withdrawal precipitated by opioid receptor antagonists. The sudden withdrawal of opioids produces a withdrawal syndrome in opioid-dependent subjects. Insulin and ATP-sensitive potassium (KATP) channel-mediated glucose homeostasis have been shown to modulate morphine withdrawal.
  
  
  OBJECTIVE
  Present study has been structured to investigate the role of insulin and pharmacological modulator of KATP channel (gliclazide) in experimental morphine withdrawal syndrome, both invivo and invitro.
  
  
  METHODS
  In this study, naloxone-precipitated morphine withdrawal syndrome in mice (invivo) as well as in rat ileum (invitro) were utilized to assess opioid withdrawal phenomenon. Morphine withdrawal syndromes like jumping and rearing frequency, forepaw licking, circling, fore paw tremor, wet dog shake, sneezing, overall morphine withdrawal severity (OMWS), serum glucose, brain malondialdehyde (MDA), glutathione (GSH), nitrite/nitrate, and calcium (Ca(+2)) were assessed.
  
  
  RESULTS
  Naloxone has significantly increased morphine withdrawal syndrome, both invivo and invitro. Insulin and gliclazide have significantly attenuated, naloxone induced behavioral changes like jumping and rearing frequency, forepaw licking, wet dog shake, sneezing, straightening, circling, OMWS, and various biochemical impairments such as serum glucose, brain MDA, GSH, nitrite/nitrate, and Ca(+2) in morphine-dependent animals (invivo). In vitro, insulin and gliclazide have significantly reduced naloxone-induced contraction in morphine-withdrawn rat ileum preparation.
  
  
  CONCLUSIONS
  Insulin and gliclazide (KATP channel blocker) have attenuated naloxone-precipitated morphine withdrawal syndrome, both invivo and invitro. Thus, insulin and KATP channel modulation may provide new avenues for research in morphine withdrawal.
authors: Neuropharmacology Laboratory, Department of Pharmacology, School of Pharmacy, Bharat Institute of Technology, Partapur Bypass, Meerut, 250103, Uttar Pradesh, India.
authors: Prabhat
authors: P
authors: Singh
authors: Bhupesh
authors: B
authors: Sharma
authors: Surbhi
authors: S
authors: Gupta
authors: B M
authors: BM
authors: Sharma
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004347:Drug Interactions; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D054086:KATP Channels / Q000378:metabolism*; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009021:Morphine Dependence / Q000188:drug therapy* / Q000378:metabolism; D009270:Naloxone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D007328:Insulin; D054086:KATP Channels; D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D009020:Morphine