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- Title
In vivo and in vitro attenuation of naloxone-precipitated experimental opioid withdrawal syndrome by insulin and selective K channel modulator.
- Authors
Singh, Prabhat; Sharma, Bhupesh; Gupta, Surbhi; Sharma, B.
- 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 (K) 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 K 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) 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 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 In vitro, insulin and gliclazide have significantly reduced naloxone-induced contraction in morphine-withdrawn rat ileum preparation.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 (K channel blocker) have attenuated naloxone-precipitated morphine withdrawal syndrome, both invivo and invitro. Thus, insulin and K channel modulation may provide new avenues for research in morphine withdrawal.
- Subjects
NALOXONE; DRUG withdrawal symptoms; OPIOID abuse; PHYSIOLOGICAL effects of insulin; PHYSIOLOGICAL effects of potassium channels
- Publication
Psychopharmacology, 2015, Vol 232, Issue 2, p465
- ISSN
0033-3158
- Publication type
Article
- DOI
10.1007/s00213-014-3680-5