Overriding the blockade of antinociceptive actions of opioids in rats treated with extended-release naltrexone

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• 作者：Reginald L. Dean ; Mark S. Todtenkopf ; Daniel R. Deaver ; Mahin F. Arastu ; Nan Dong ; Krystal Reitano ; Kevin O'Driscoll ; Kristina Kriksciukaite ; David R. Gastfriend
• 关键词：XR-NTX ; Analgesia ; Antinociception ; Morphine ; Fentanyl ; Hydrocodone ; Respiration rate ; Locomotor activity ; Vivitrol® ; PLG microspheres
• 刊名：Pharmacology Biochemistry and Behavior
• 出版年：2008
• 出版时间：June 2008
• 年：2008
• 卷：89
• 期：4
• 页码：515-522
• 全文大小：241 K

文摘

A monthly extended-release formulation of the opioid antagonist naltrexone (XR-NTX) is approved for treatment of alcohol dependence. There is little research regarding overriding chronic (> 21 days) competitive opioid receptor blockade with opioids for acute pain. Using the hot plate test after XR-NTX or placebo microsphere administration, rats were treated with an opioid analgesic to determine the dose required to produce the maximum response latency (MRL; 60 s). Rats were later treated with the same opioid to determine any potential effects on respiration rate or locomotor activity. In naïve rats, 15 mg/kg morphine, 0.1 mg/kg fentanyl and 8 mg/kg hydrocodone produced MRL. In XR-NTX treated rats, morphine produced 36 % and 46 % MRL at 90 mg/kg on days 4 and 19 and 96 % MRL at 45 mg/kg on day 39. Fentanyl produced 100 % MRL at 2.0 mg/kg on days 4 and 19 and at 0.5 mg/kg on day 39. Hydrocodone (80 mg/kg) produced 69 % , 80 % and 100 % MRL on days 4, 19 and 39. Compared to placebo, these doses did not further depress respiration or alter locomotor activity. Thus, opioid receptor blockade with XR-NTX can be overcome in rats with higher doses of opioids without further affecting respiration or locomotor activity.