Access to running wheels attenuates spontaneous morphine withdrawal in mice as measured by thermal sensitivity.

摘要

Opioid withdrawal is a critical component of opioid abuse and consists of a wide array of symptoms. For many people, the presence of, or desire to avoid, these withdrawal symptoms drives continued drug taking. There is growing evidence that aerobic exercise may be a positive intervention during the withdrawal period. The following studies seek to develop a behavioral procedure to examine one component of spontaneous opioid withdrawal in mice, hypersensitivity to a thermal stimulus, and to examine the effects of access to a running wheel during withdrawal. The experiments of Chapter 2 describe and validate the spontaneous withdrawal procedure. During the first 48 hours following the cessation of 30, 56, or 100 mg/kg morphine response latency on a hotplate is significantly decreased suggesting an increase in thermal sensitivity. The experiments described in Chapter 3 demonstrate that access to a running wheel during withdrawal reduced this increase in thermal sensitivity. Chapter 4 extended the previous results, assessing the effect of a locked wheel and group housing during withdrawal. The results provide evidence that use of the wheel not simply environmental enrichment maximized the effect on thermal sensitivity. The experiments of Chapter 5 sought to further probe the effects of wheel access. Morphine's potency was assessed following 6 weeks of wheel access or chronic morphine injections. Under both conditions, tolerance to the antinociceptive effects of morphine developed. Immediately following behavioral testing, changes in the expression of five genes associated with the opioid system was assessed using qRT-PCR. The experimental results descried in this dissertation suggest that thermal sensitivity is a reliable and sensitive measure of spontaneous morphine withdrawal in mice and that wheel access can attenuate this sign of withdrawal.