In vivo and in vitro attenuation of naloxone-precipitated experimental opioid withdrawal syndrome by insulin and selective KATP channel modulator
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- 作者：Prabhat Singh (1)
Bhupesh Sharma (2) (3)
Surbhi Gupta (1)
B. M. Sharma (2)
1. Neuropharmacology Laboratory ; Department of Pharmacology ; School of Pharmacy ; Bharat Institute of Technology ; Partapur Bypass ; Meerut ; 250103 ; Uttar Pradesh ; India
2. Department of Pharmacology ; School of Pharmacy ; Bharat Institute of Technology ; Partapur Bypass ; Meerut ; 250103 ; Uttar Pradesh ; India
3. CNS Pharmacology ; Conscience Research ; Pocket F-233 ; B ; Dilshad Garden ; Delhi ; 110095 ; India - 关键词：Morphine ; Jumping ; Circling ; Forepaw licking ; Glucose ; Nitrite/nitrate ; Malondialdehyde ; Glutathione ; Calcium
- 刊名：Psychopharmacology
- 出版年：2015
- 出版时间：January 2015
- 年：2015
- 卷：232
- 期：2
- 页码：465-475
- 全文大小：382 KB
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- 刊物主题：Biomedicine
Pharmacology and Toxicology
Psychiatry - 出版者：Springer Berlin / Heidelberg
- ISSN：1432-2072
文摘
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.