Browsing by Subject "self-administration"
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Item Characterization of Morphine Self-Administration Following Spinal Cord Injury(2013-07-16) Woller, Sarah AnnApproximately two-thirds of patients will experience pain following spinal cord injury (SCI). This pain can arise as an immediate consequence of SCI, or can develop over time into chronic, neuropathic pain. Individuals are frequently prescribed opioid analgesics, including morphine, for the treatment of pain in both the acute and chronic phases of SCI. Yet, despite the prevalence of opioid use, no studies have examined the addictive potential of opioids, or their secondary effects, following spinal injury. These experiments used a clinically relevant self-administration paradigm to examine both addiction and functional recovery after morphine administration. To assess morphine administration in the acute phase of SCI, animals were placed in operant chambers 24-hours following spinal injury. In the chambers, depression of a reinforced lever resulted in an intravenous infusion of morphine (or vehicle). Animals were placed in the chambers for 7, 12-hour sessions and could administer up to 30 mg of morphine per session. Morphine self-administration was also examined in the chronic phase of injury. Animals were placed into operant chambers for 7, 12-hour sessions beginning 14 or 35 days after injury. The amount of morphine administered, as well as recovery of locomotor function and general health, was compared across subjects with SCI and sham (no injury) controls. In the acute phase of injury, SCI significantly reduced self-administration of morphine, but administration led to decreased recovery of locomotor function and weight loss. In the chronic phase of injury, self-administration did not differ between contused and sham animals. All subjects administered the full amount of morphine available each day. In this phase of injury, morphine administration led to significant weight loss, but did not attenuate recovery of locomotor function. These studies suggest that spinal injury reduced the addictive potential of morphine in the acute, but not the chronic, phase of SCI. However, acute administration of high doses of morphine decreased recovery of locomotor function. Morphine should not be used in this phase of injury for the clinical treatment of pain. In the chronic phase, opioid use must be closely monitored as use may result in addictive behavior.Item Methamphetamine self-administration in rats developmentally exposed to lead(2009-05-15) Rocha, AngelicaMethamphetamine is gaining mainstream popularity across the United States at the same time that lead exposure remains at elevated levels. Perinatal (gestation/lactation) lead exposure has been found to modify the reward efficacy of various drugs of abuse (e.g., cocaine, opiates) across the phases of initial selection, use, and abuse. Lead-induced changes in sensitivity to methamphetamine have not been examined in animals perinatally exposed to lead. Accordingly, four studies were conducted to examine the effects of perinatal lead exposure on adult self-administration of intravenous (i.v.) methamphetamine across all relevant transition points of drug addiction. Adult female rats were administered a 16-mg lead or a control solution for 30 days prior to breeding with non-exposed males. Exposure continued through pregnancy and lactation and was discontinued at weaning (postnatal day [PND] 21). Animals born to control or lead-exposed dams received indwelling jugular catheters as adults (PND 60 and PND 90) and subsequently were randomly assigned to one of the four studies mentioned above, using only one male rat per litter for each study. In Experiment 1, an acquisition study revealed that perinatal exposure to environmentally relevant levels of lead resulted in a smaller percentage of rats reaching the criterion for intravenous (i.v.) methamphetamine (.02 mg/kg) acquisition, relative to non-exposed controls. In Experiment 2, a dose-effect curve yielded a biphasic pattern of attenuation of the self-administration of methamphetamine (.04 mg/kg) in lead-exposed animals. In Experiment 3, lead-exposed animals reached lower breaking points for methamphetamine (.04 mg/kg) in a progressive ratio task, in comparison to control animals. Finally in Experiment 4, a reinstatement study revealed that perinatally leadexposed animals showed a decreased propensity to relapse to methamphetamine (.04 mg/kg) self-administration after a period of forced abstinence. The general attenuation to the rewarding efficacy of methamphetamine observed in animals perinatally exposed to lead may functionally translate into a form of tolerance or counteradaptation. The data collected from these four studies further strengthen the possibility that pollutants in the environment may play a modulatory role in substance abuse.