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Establishing a time course for spontaneous opioid withdrawal in male and female outbred mice using an abbreviated dependence paradigm
Author(s) -
Quock Raymond Mark,
Brewer Abigail Lucille
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.663.6
Subject(s) - opioid , drug withdrawal , kindling , morphine , naltrexone , medicine , addiction , withdrawal syndrome , anesthesia , opioid antagonist , antagonist , psychology , pharmacology , psychiatry , receptor , (+) naloxone , drug , stimulation
Opioid withdrawal is often a limiting factor in recovery from opioid dependence due to negative reinforcement caused by continued use of opioids in order to avoid the distressing withdrawal symptoms. In animal models of dependence, opioid withdrawal is frequently precipitated using opioid antagonists and the severity of withdrawal is related to the level of dependence. However, this model lacks face validity when investigating new treatment possibilities for opioid withdrawal because most human addicts are not exposed to an antagonist in order to precipitate withdrawal. Furthermore, results from animal experiments suggest that spontaneous and precipitated withdrawal involve different mechanisms and may favor different symptoms of withdrawal. These experiments were conducted to investigate the timeline of spontaneous withdrawal in an outbred mouse model using an abbreviated dependence paradigm. Male and female NIH Swiss mice were injected with escalating doses of morphine twice daily (50–125 mg/kg morphine) over a period of four days. On the fifth day, mice were given a final dose of morphine and withdrawal symptoms were assessed at 5, 10, 24, 34, 48, 58, 72, 82, 96, and 106 hrs after the final injection. Withdrawal symptoms were assessed by global scores for an overall picture and by counting the number of tremors, wet dog shakes, and jumps. Results showed a robust withdrawal time course that peaked at 24 hrs in both sexes as assessed by global score. When broken down, wet dog shakes and tremors proved to be the most reliable indicator of severity of withdrawal and females showed more tremors than males for the 1 st 24 hours of the time course. These results establish a spontaneous withdrawal time course in an outbred strain of mouse that shows that dependence can be reliably established over a four‐day period using fairly high escalating doses of morphine. Furthermore, these results suggest that individual symptoms of withdrawal should be assessed over time as well as global score. Support or Funding Information Supported in part by the State of Washington Initiative Measure No.171. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .