Opioid abuse and addiction affects more than 2.4 million people in the United States. Medication assisted treatment (MAT), in combination with counseling, is recognized as the most effective treatment for patients with opioid dependence and abuse. Although MAT is considered the most effective treatment, previous research has found clinically significant weight gain with methadone. The purpose of this study was to determine if hedonic eating behaviors, sugar cravings, and addictive like eating was related to weight gain in opioid addicted patients receiving methadone and buprenorphine/naloxone (Suboxone™). Hedonic eating behaviors were measured using three validated surveys. Following survey collection, a chart review was completed to determine weight changes over time. One hundred twenty surveys were completed and 113 were analyzed. No differences were found between the medication groups in terms of mean age, weight at entry, BMI at entry, race, sex, and Hepatitis C status. A subset of 39 participants was analyzed for weight changes during treatment. There were no differences in food addiction scores, hedonic eating behaviors, and food cravings between the medication groups. We found significant weight gain in patients receiving methadone and no weight changes for those receiving Suboxone™. Weight gain in methadone maintenance does not appear to be related to addictive like eating, food craving, or hedonic eating. This research suggests that weight gain seen in methadone maintenance for opioid addiction treatment is related to something other than hedonic eating behaviors. Clinically significant weight gain should be considered when prescribing methadone for opioid addiction.

There are currently many opioid agonists available for clinical use as analgesics. However, many of these opioid agonists have notorious side effects including respiratory depression and may lead to addiction and dependence. Problems associated with these opioid agonists are determined to come from their interactions with the mu-opioid receptor. Opioid antagonists, such as naltrexone, have shown to aid in the treatment of opioid addiction. Although naltrexone has high affinity to the mu-opioid receptor, it lacks selectivity. Novel selective mu-opioid receptor antagonists were designed based on the identification of important pharmacophore elements in several known mu-opioid receptor agonists and antagonists. These compounds were synthesized and in vitro biological assays were conducted to determine their affinity to all three opioid receptors. Also, molecular modeling studines were conducted to help visualize the interactions between the mu-opioid receptor and these ligands. Finally, four lead compounds have been identified for further optimization.

The purpose of this study was to describe involvement in everyday activities for people with opioid replacement therapy. To answer the purpose, an empirical qualitative design was chosen that is appropriate for capturing a person's own thoughts, feelings, experiences, experiences and opinions and the world in which he lives with the person's own words. Data were collected through interviews with people who have opioid replacement therapy. The collected data consisted of six interviews analyzed based on a latent qualitative content analysis. Analysis of data resulted in an overall theme; Living in life does not survive life and four categories; A struggle to adapt to something new and find structure in everyday life. To dare to believe in his ability. To get professional support along the way. The importance of the social environment for breaking old life. The result showed that involvement in everyday activities is a major challenge and a struggle that depends both on the support people receive from care and social services in their change process, their confidence in their own ability and how to succeed in creating a new identity and how the social environment around them look. Conclusions that can be deduced from the results of the study can give implications for people who have opioid replacement therapy to help build new life in addition to receiving medication. It is a struggle to adapt and create a new identity and in that work, occupational therapy can perform an important role. / Syftet med denna studie var att beskriva engagemang i vardagliga aktiviteter för personer med läkemedelsassisterande behandling vid opiatberoende. För att besvara syftet valdes en empirisk kvalitativ design som är lämpligt för att fånga en persons egna tankar, känslor, upplevelser, erfarenheter och åsikter och den värld den lever i med personens egna ord. Data insamlades genom intervjuer med personer som har läkemedelsassisterande behandling vid opiatberoende. Insamlad data bestod av sex intervjuer som analyserades utifrån en latent kvalitativ innehållsanalys. Analys av data resulterade i ett övergripande tema; Att leva i livet inte överleva livet och fyra kategorier; En kamp att anpassa sig till något nytt och finna struktur i vardagen. Att våga tro på sin förmåga. Att få professionellt stöd på vägen. Den sociala miljöns betydelse för att kunna bryta med det gamla livet. Resultatet visade att engagemang i vardagliga aktiviteter är en stor utmaning och en kamp som både beror på vilket stöd personerna får av vård och socialtjänst i sin förändringsprocess, deras tilltro till sin egen förmåga och hur det lyckas skapa en ny identitet samt hur den sociala miljön runt dem ser ut.  Slutsatser som kan dras utifrån studiens resultat kan ge implikationer för att personer som har läkemedelsassisterande behandling vid opiatberoende vill ha hjälp med att bygga upp det nya livet utöver att de får mediciner. Det är en kamp att anpassa sig och skapa en ny identitet och i det arbetet kan arbetsterapi spela en viktig roll.

Rhes (Ras homolog enriched in striatum) has been identified as a novel monomeric G-protein involved in dopaminergic and other signaling in the striatum. Given the many effects of opioids that involve striatal circuitry, genetically engineered mice that are incapable of making Rhes (rhes-/-) and their control littermates (rhes+/+) were subjected to behavioral tests to determine if any differences existed in opioid analgesia, tolerance, withdrawal, reward, and locomotion. Rhes-/- mice showed an increased opioid mediated analgesia, along with an absence of tolerance and decrease in withdrawal when compared with rhes+/+ littermates. However, no significant changes were seen in opioid induced locomotor activation or conditioned place preference. These results provide strong evidence for the implication of Rhes in opioid signaling.

Thesis advisor: Alexa H. Veemena / Across species, the juvenile period is characterized by increased social interaction with peers and heightened novelty-seeking behavior, as compared to any other life stage. These behaviors are likely to be highly adaptive during this developmental phase. Still, an excessive novelty-seeking phenotype may predispose individuals to risk-taking and substance abuse, while too little social engagement and low novelty-seeking are characteristics of neuropsychiatry disorders such as autism. The over-arching aim of this dissertation research has been to elucidate the neural mechanisms underlying juvenile social novelty-seeking behavior. Central activation of oxytocin, vasopressin V1a, and µ-opioid receptors (OTR, V1aR, and MOR, respectively) have been implicated in the regulation of adult social behavior, but our understanding of the expression and function of OTR, V1aR, and MORs in the juvenile brain is incomplete. Therefore, in Studies 1 and 2, age differences in binding density of OTR, V1aR, and MOR throughout the rat brain were identified using receptor autoradiography. Next, in Study 3, I established the social novelty preference test, a new paradigm designed to assess the preference of juvenile rats to interact with either a novel or a familiar (cage mate) conspecific. Using this social novelty preference test, in Studies 3, 4, and 5, the functional involvement of OTR, V1aR, and MOR in the regulation of juvenile social novelty preference was characterized using both intracerebroventricular and local in-vivo pharmacological manipulations. The results of these experiments demonstrate that both OTR and MOR activation in the brain are involved in the regulation of juvenile social novelty preference, particularly acting within the nucleus accumbens. Finally, in Study 5, I investigated the impact of social isolation on juvenile social novelty preference. My findings show that social isolation potently reduces social novelty preference, which, in turn, can be restored by MOR activation in the nucleus accumbens. Taken together, this body of work significantly advances our understanding of the neural systems underlying juvenile social novelty preference, and suggests that both oxytocin and opioid systems in the brain may be potential clinical targets for restoring social novelty-seeking behavior in neurodevelopmental disorders, such as autism.

Made available in DSpace on 2014-06-11T19:22:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2008-04-30Bitstream added on 2014-06-13T20:28:37Z : No. of bitstreams: 1 albuquerque_vb_me_araca.pdf: 508052 bytes, checksum: f5bfe0202134876e0b52b05728bc52f8 (MD5) / A utilização da anestesia local peridural tem alcançado grande ênfase nos últimos anos, sobretudo com a utilização de opióides. O presente trabalho teve como objetivo investigar a utilização da ropivacaína isolada ou em associação a diferentes opióides, na anestesia peridural de cadelas submetidas à ovariosalpingohisterectomia (OSH) eletiva. Participaram do estudo duplamente encoberto 32 cadelas sadias, adultas, de diferentes raças, pesando entre seis e 15 kg e pré-medicadas com acepromazina (0,05mg/kg, IM) associada ao midazolam (0,2mg/kg, IM), distribuídas em quatro grupos distintos: Grupo 1: ropivacaína: 0,3 mL/kg; Grupo 2: ropivacaína + morfina (0,1 mg/kg); Grupo 3: ropivacaína + butorfanol (0,1 mg/kg); e Grupo 4: ropivacaína + tramadol (0,5 mg/kg) administrados pela via peridural. Em cada momento experimental foram mensurados: freqüência cardíaca; freqüência respiratória; pressão arterial sistólica; temperatura retal; pressão parcial dos gases sangüíneos (arterial); pH sangüíneo; além da avaliação não-paramétrica do grau de sedação, grau de sangramento e de relaxamento muscular seguindo tabelas de escores. Os dados foram submetidos à ANOVA e comparados pelos testes de Kruskal-Wallis, Friedman, Dunn e Tukey (p< 0,05). Concluiu-se que a utilização da ropivacaína isolada ou associada à morfina, ao butorfanol ou ao tramadol pela via peridural não promoveu depressão cardiorrespiratória ou alterações hemodinâmicas significativas, sendo que a ropivacaína associada ao butorfanol permitiu a realização de OSH em cadelas. / The use of epidural local anesthesia has been reaching great emphasis for the last years, overcoat with the opioids using. This research ained the use of ropivacaine with or without association the different opioids, for epidural anesthesia biches submitted the elective ovariosalpingohisterectomy (OSH). 32 bitches tool part is this double-blind study, adult, different breed, weighing between 6 and 15kg and pré-medicated with acepromazine (0.05mg/kg, IM) associated to the midazolam (0.2mg/kg, IM), distributed in for different groups: Group 1: ropivacaine: 0.3 mL/kg; Group 2: ropivacaine + morphine (0.1 mg/kg); Group 3: ropivacaine + butorphanol (0.1 mg/kg); and Group 4: ropivacaine + tramadol (0.5 mg/kg) administered epidural. The following parameters were studied: heart frequency; breathing frequency; systolic arterial pressure; rectal temperature; blood gas partial pressures (arterial); blood pH; besides non-parametric of sedation grade, bleeding grade and muscular relaxation following tables scores. The results were submitted by ANOVA and compared by Kruskal-Wallis, Friedman, Dunn and Tukey test (p< 0.05). It was conclude that the use of only ropivacaine or associated with morphine, with butorphanol or tramadol for the epidural administration didn't promote depression cardiorrespiratory or significant hemodinamycs alterations and the ropivacaine associated to the butorphanol allowed OSH in bitches accomplishment.

Mu opioid receptors (MOPs) in the pain pathway contribute to morphine analgesia. Morphine also stimulates reward/reinforcement through disinhibition of dopaminergic (DA) neurones in the ventral tegmental area (VTA), an effect implicated in its abuse and dependence. We hope to develop approaches to achieve sustained analgesia without affecting reward by exploiting differential MOP signalling mechanisms in the pain and reward pathways. MOPs, delta opioid receptors (DOPs) and β-arrestin2 (BAR2) are all necessary components of the signalling complex in nociceptive neurones for morphine analgesic tolerance; c-Src (a tyrosine kinase), thought to couple to MOP receptors through BAR2 has also been implicated. To investigate opioid receptor signalling in response to morphine we used a variety of different techniques that included behavioural measures of nociception, reinforcement and locomotion and electrophysiological methods to study DRG neurones from the pain pathway and brain slices containing VTA neurones. This study in mice confirms that morphine administered subcutaneously (SC) causes analgesia, analgesic tolerance, and has psychomotor effects leading to enhanced locomotion and reinforcement. In VTA neurones morphine and the selective MOP receptor agonist DAMGO caused concentration-dependent inhibition of the frequency of IPSCs. All these actions of morphine were absent from MOP-/- mice. Morphine exhibited reduced potency as 1) an analgesic, 2) stimulator of locomotion, 3) a reinforcer in CPP and 4) an inhibitor of sIPSC frequency, when applied to MOP+/- mice or their VTA neurones. Morphine analgesic tolerance developed faster and to a greater extent in MOP+/- mice than in WT mice. DOP-/- mice exhibited morphine analgesia with less tolerance, as did BAR2-/- mice. BAR2-/- mice also exhibited reduced morphine locomotion and an increased sensitivity to morphine reinforcement. Morphine tolerance was absent from BAR2-/-//DOP-/- mice. The inhibition of sIPSC frequency by morphine was reduced in BAR2+/- and BAR2-/- VTA neurones. Dasatinib and PP2 (c-Src tyrosine kinase inhibitors) prevented the development of morphine tolerance in WT and MOP+/- mice and dasatinib caused its reversal in the latter. The drugs had no significant analgesic effect alone. Dasatinib did not affect morphine preference or locomotor activation. PP2 reduced morphine’s inhibition of sIPSC frequency. As c-Src inhibition does not appear to alter the psychomotor effects produced by morphine and it acts to reduce morphine analgesic tolerance. We believe that cSrc is an attractive target to prevent the development of morphine analgesic tolerance without affecting hedonic homeostasis.

Abstract available through Clinical Pharmacology in Drug Development.

Abstract available through Clinical Pharmacology in Drug Development.

abstract: Opioid use in the United States is skyrocketing. Overdose deaths have increased 433% in the last decade and will continue climbing. In addition to the mortality caused by illicit opioid misuse, morbidity rates have also risen. People Who Inject Drugs (PWID) demonstrate higher rates of Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), Endocarditis, Persistent Abscesses, Staphylococcus Aureus (S. aureus, Staph) and other skin infections. This thesis serves as (1) a systematic review of the differences in health conditions experienced by PWID and (2) an examination of the trends in skin and soft tissue infection from a small sample in Phoenix, Arizona. The author argues that PWID suffer from an increased rate of comorbid conditions associated with substance use. Targeted social work interventions could be useful in reducing the rates of disease and their impact on the individual and community. / Dissertation/Thesis / Masters Thesis Social Work 2019