Prabhat Singh1, Bhupesh Sharma, Surbhi Gupta, B M Sharma. 1. Neuropharmacology Laboratory, Department of Pharmacology, School of Pharmacy, Bharat Institute of Technology, Partapur Bypass, Meerut, 250103, Uttar Pradesh, India.
Abstract
RATIONALE: 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 In vitro, insulin and gliclazide have significantly reduced naloxone-induced contraction in morphine-withdrawn rat ileum preparation.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.
RATIONALE: 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 morphinewithdrawal syndrome, both invivo and invitro. METHODS: In this study, naloxone-precipitated morphinewithdrawal 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 morphinewithdrawal 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 morphinewithdrawal syndrome, both invivo and invitro. Thus, insulin and KATP channel modulation may provide new avenues for research in morphine withdrawal.
Authors: Franklin A Lee; Brandon A Baiamonte; Daniela Spano; Gerald J Lahoste; R Denis Soignier; Laura M Harrison Journal: Neurosci Lett Date: 2010-12-14 Impact factor: 3.046
Authors: Harun Alp; Sefer Varol; Muhammet Murat Celik; Murat Altas; Osman Evliyaoglu; Orhan Tokgoz; Mehmet Halis Tanrıverdi; Ertugrul Uzar Journal: Exp Diabetes Res Date: 2012-01-16