Browsing by Subject "morphine"
Now showing 1 - 3 of 3
Results Per Page
Sort Options
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 MicroRNA Dysregulation Following Spinal Cord Contusion: Implications for Neural Plasticity and Neuropathic Pain(2013-05-30) Strickland, EricSpinal cord injury (SCI) results in a number of devastating consequences, including loss of motor function, paralysis, and neuropathic pain. Concomitant peripheral tissue injury below the lesion site can result in uncontrollable nociception that sensitizes spinal neurons and promotes chronic pain. Additionally, drugs like morphine, though critical for pain management, elicit pro-inflammatory effects that exacerbate chronic pain symptoms. Currently, there is a lack of effective therapeutic mechanisms to promote regeneration at the lesion site, and a limited understanding of regulatory mechanisms that can be utilized to therapeutically manipulate spinal cord plasticity. MicroRNAs (miRNAs) constitute novel targets for therapeutic intervention to both promote repair and regeneration, and mitigate maladaptive plasticity that leads to neuropathic pain. Microarray and qRT-PCR comparisons of contused and sham rat spinal cords at 4 and 14 days following SCI indicated that a total of 35 miRNAs were dysregulated, with miR1, miR124, and miR129 exhibiting significant down-regulation after SCI, and both miR21 and miR146a being transiently induced. Localized expression of miRNAs and cellular markers indicated that changes in miRNA regulation favor the emergence of neural stem cell niches and reversion of surviving neurons to a pre-neuronal phenotype. Additionally, both uncontrollable nociception and morphine administration resulted in further dysregulation of SCI-sensitive miRNAs, along with their mRNA targets. Morphine administration significantly induced expression of both miR21 and IL6R expression, indicating that morphine-induced miRNA dysregulation is involved in the promotion of neuroinflammation that drives increased pain-sensitivity. Similarly, uncontrollable nociception significantly modulates expression of miR124, miR129, and miR146a, which inhibit cell cycle proteins and microglial activation, and dysregulation of these miRNAs, along with BDNF and IGF-1, likely contributes towards promotion of hypersensitivity in spinal neurons that underlies neuropathic pain. Consequently, SCI- sensitive miRNAs may constitute therapeutic targets for modulation of neuroinflammation and microglial activation in order to mitigate secondary injury, promote regeneration, and prevent maladaptive plasticity that drives neuropathic pain and exacerbation of chronic pain symptoms by morphine administration.Item Social environment modulates morphine sensitivity: A partial role of vasopressin V1b receptor(2012-08-31) Hofford, Rebecca 1983-Social factors influence drug abuse in adolescents; this is partially attributed to peer pressure in humans. Similarly, using rodent models, some research suggests that social housing condition can influence rodents' drug taking behavior. Despite this, few studies have examined the role that intoxicated peers have on drug-naive cage-mates. This dissertation examined how social environment affects opioid sensitivity and hormone production. This was accomplished by comparing the opioid sensitivity of mice housed in mixed cages (some animals received opioids and some were drug-naive) to cages where all the mice were treated with the same drug (all saline or all morphine). These studies identified an adolescent-specific vulnerability to social environment-induced alteration of morphine sensitivity. Interaction with drug-intoxicated cage-mates enhanced locomotor sensitivity in previously drug-naive males and altered their production of testosterone. Conversely, interaction of morphine experienced mice with drug-naive cage-mates afforded protection from the rewarding properties of morphine. In other words, morphine-treated mice housed with drug-naive cage-mates demonstrated attenuated reward compared to morphine-treated mice housed with other morphine-treated mice. In addition, part of the neurobiological basis of the social-environment effect was identified. Antagonism of V1b receptors decreased morphine reward in morphine-treated mice housed only with other morphine-treated mice. These results suggest a role of vasopressin in the peer influence on drug sensitivity observed in adolescents. This body of work further elucidates the role of peer influence on opioid sensitivity. Future studies should further reveal the role of healthy peer relationships and should aid in combating drug abuse in this at-risk demographic.