Abstract
Opioid analgesics are among the most effective agents for treatment of moderate to severe pain. However, the use of morphine after a spinal cord injury (SCI) can potentiate the development of paradoxical pain symptoms, and continuous administration can lead to dependence, tolerance, and addiction. Although some studies suggest that the addictive potential of morphine decreases when it is used to treat neuropathic pain, this has not been studied in a SCI model. Accordingly, the present studies investigated the addictive potential of morphine in a rodent model of SCI using conditioned place preference (CPP) and intravenous self-administration paradigms. A contusion injury significantly increased the expression of a CPP relative to sham and intact controls in the acute phase of injury. However, contused animals self-administered significantly less morphine than sham and intact controls, but this was dose-dependent; at a high concentration, injured rats exhibited an increase in drug-reinforced responses over time. Exposure to a high concentration of morphine impeded weight gain and locomotor recovery. We suggest that the increased preference observed in injured rats reflects a motivational effect linked in part to the drug's anti-nociceptive effect. Further, although injured rats exhibited a suppression of opiate self-administration, when given access to a high concentration, addictive-like behavior emerged and was associated with poor recovery.