Heroin dependence, which is escalating within South Africa, has become a symbol of the social disorder of the times - associated with materialism, poverty, crime, the problems of a society in transition, the disadvantaged, and the inner cities. However, that is not to say that all those who misuse heroin develop a problem or become dependent. In reality, only a small minority of heroin users develop a dependence, but for those who do it can result in unpleasant and potentially terrifying experiences/consequences, that can often be extremely difficult to escape from. That is not to say that recovery from dependence to heroin is not possible. Indeed, contrary to the beliefs of many people, the reality is that many people do eventually recover. Despite the vast sums of money devoted to treatment intervention of heroin dependants in the South Africa and worldwide, the processes by which recovery occur remain fairly unclear. Moreover, relatively little is known about the contribution of interventions and processes in facilitating such recovery. The statistical and content analysis of the data revealed that one of the most important factors identified in allowing successful behaviour modification and promoting recovery was psychosocial and pharmacological intervention, which seemed to produce a range of positive effects that facilitated natural healing processes. However, a range of other factors alongside intervention were also important in promoting behaviour modification. This study has provided important information, from forty recovering heroin dependants themselves, on the many factors that are important in achieving abstinence, in allowing recovery to be maintained in the longer term, and in potentially allowing an eventual exit from heroin dependence. A number of difficulties encountered in intervention were also identified. The statistical findings of the study support the `maturing out' hypothesis of heroin dependence (c² = 16.841; r = 0.001; df = 3). Ethnicity, highest level of education, employment status, marital status, biological parents' marital status or whether biological parents were deceased or not did not relate to any of the identified behavioural indices associated with heroin dependence recovery. A framework for the development of a contextual heroin dependence recovery model is also discussed. / Psychology / (M.A.(Psychology))

The history of heroin use disorder intervention has been characterised by fads and fashions. Some of the treatments that have been used have been, at best ineffective, and at worst harmful, and occasionally even dangerous. It is a sad reflection upon the field that practices and procedures for the treatment of heroin use disorders can so easily be introduced and applied without (or even contrary to) evidence. In South Africa, the field of heroin use disorder intervention has been `in transition' since the outbreak of the heroin epidemic. Yet despite growing evidence of an association between heroin dependents use of supplementary intervention services (such as psychosocial and pharmacological/medical care) and intervention outcomes, and the fact that international emerging standards for substance use disorder intervention have called upon treatment intervention providers to enhance traditional substance use disorder services with services that address clients' psychological and social needs, heroin use disorder intervention programmes in South Africa generally fail to meet these research-based intervention standards. Much of what is currently delivered as intervention is based upon current best guesses of how to combine some science-based (for example, cognitive-behavioural therapy and pharmacotherapies) and self-help (12-step programmes) approaches into optimal intervention protocols. As progression is made in the twenty-first century, scientific information is now beginning to be used to guide the evolution and delivery of heroin use disorder care internationally. Regrettably, a scarcity of heroin use disorder intervention research is noted in South Africa. The present study delved into the insights of ten heroin use disorder specialists, and synthesised the findings with the results of a previous study undertaken by the author relating to forty long-term voluntarily abstinent heroin dependents. In terms of theory and practice, findings of the study suggest that the field is less in transition now than it was in 1995. It is an imperative that law-enforcement action be followed by an integrated programme of psychological, social and pharmacological outreach. These programmes will have to be expanded to address new demands and will need to include specialised skills training. Many interventions and procedures have begun to be integrated routinely into clinical practice. / Psychology / (D. Phil. (Psychology))

Heroin dependence, which is escalating within South Africa, has become a symbol of the social disorder of the times - associated with materialism, poverty, crime, the problems of a society in transition, the disadvantaged, and the inner cities. However, that is not to say that all those who misuse heroin develop a problem or become dependent. In reality, only a small minority of heroin users develop a dependence, but for those who do it can result in unpleasant and potentially terrifying experiences/consequences, that can often be extremely difficult to escape from. That is not to say that recovery from dependence to heroin is not possible. Indeed, contrary to the beliefs of many people, the reality is that many people do eventually recover. Despite the vast sums of money devoted to treatment intervention of heroin dependants in the South Africa and worldwide, the processes by which recovery occur remain fairly unclear. Moreover, relatively little is known about the contribution of interventions and processes in facilitating such recovery. The statistical and content analysis of the data revealed that one of the most important factors identified in allowing successful behaviour modification and promoting recovery was psychosocial and pharmacological intervention, which seemed to produce a range of positive effects that facilitated natural healing processes. However, a range of other factors alongside intervention were also important in promoting behaviour modification. This study has provided important information, from forty recovering heroin dependants themselves, on the many factors that are important in achieving abstinence, in allowing recovery to be maintained in the longer term, and in potentially allowing an eventual exit from heroin dependence. A number of difficulties encountered in intervention were also identified. The statistical findings of the study support the `maturing out' hypothesis of heroin dependence (c² = 16.841; r = 0.001; df = 3). Ethnicity, highest level of education, employment status, marital status, biological parents' marital status or whether biological parents were deceased or not did not relate to any of the identified behavioural indices associated with heroin dependence recovery. A framework for the development of a contextual heroin dependence recovery model is also discussed. / Psychology / (M.A.(Psychology))

Various molecular pathways in the brain shape our understanding of good and bad, as well as our motivation to seek and avoid such stimuli. This work evolves around how systemic inflammation causes aversion; and why general unpleasant states such as sickness, stress, pain and nausea are encoded by our brain as undesirable; and contrary to these questions, how drugs of abuse can subjugate the motivational neurocircuitry of the brain. A common feature of these various disease states is involvement of the motivational neurocircuitry - from mesolimbic to striatonigral pathways. Having an intact motivational system is what helps us evade negative outcomes and approach natural positive reinforcers, which is essential for our survival. During disease-states the motivational neurocircuitry may be overthrown by the molecular mechanisms that originally were meant to aid us. In study I, to investigate how inflammation is perceived as aversive, we used a behavioral test based on Pavlovian place conditioning with the aversive inflammatory stimulus E. coli lipopolysaccharide (LPS). Using a combination of cell-type specific gene deletions, pharmacology, and chemogenetics, we uncovered that systemic inflammation triggered aversion by MyD88-dependent activation of the brain endothelium followed by COX1-mediated cerebral prostaglandin E2 (PGE2) synthesis. Moreover, we showed that inflammation-induced PGE2 targeted EP1 receptors on striatal dopamine D1 receptor–expressing neurons and that this signaling sequence induced aversion through GABA-mediated inhibition of dopaminergic cells. Finally, inflammation-induced aversion was not an indirect consequence of fever or anorexia but constituted an independent inflammatory symptom triggered by a unique molecular mechanism. Collectively, these findings demonstrate that PGE2-mediated modulation of the dopaminergic circuitry is a key mechanism underlying inflammation-induced aversion. In study II, we investigate the role of peripheral IFN-γ in LPS induced conditioned place aversion by employing a strategy based on global and cell-type specific gene deletions, combined with measures of gene-expression. LPS induced IFN-ɣ expression in the blood, and deletion of IFN-ɣ or its receptor prevented conditioned place aversion (CPA) to LPS. LPS increased the expression of chemokine Cxcl10 in the striatum of normal mice. This induction was absent in mice lacking IFN-ɣ receptors or Myd88 in blood brain barrier endothelial cells. Furthermore, inflammation-induced aversion was blocked in mice lacking Cxcl10 or its receptor Cxcr3. Finally, mice with a selective deletion of the IFN-ɣ receptor in brain endothelial cells did not develop inflammation-induced aversion. Collectively, these findings demonstrate that circulating IFN-ɣ binding to receptors on brain endothelial cells which induces Cxcl10, is a central link in the signaling chain eliciting inflammation-induced aversion. In study III, we explored the role of melanocortin 4 receptors (MC4Rs) in aversive processing using genetically modified mice in CPA to various stimuli. In normal mice, robust aversions were induced by systemic inflammation, nausea, pain and kappa opioid receptor-induced dysphoria. In sharp contrast, mice lacking MC4Rs displayed preference towards most of the aversive stimuli, but were indifferent to pain. The unusual flip from aversion to reward in mice lacking MC4Rs was dopamine-dependent and associated with a change from decreased to increased activity of the dopamine system. The responses to aversive stimuli were normalized when MC4Rs were re-expressed on dopamine D1 receptor-expressing cells or in the striatum of mice otherwise lacking MC4Rs. Furthermore, activation of arcuate nucleus proopiomelanocortin neurons projecting to the ventral striatum increased the activity of striatal neurons in a MC4R-dependent manner and elicited aversion. Our findings demonstrate that melanocortin signaling through striatal MC4Rs is critical for assigning negative motivational valence to harmful stimuli. The neurotransmitter acetylcholine has been implied in reward learning and drug addiction. However, the role of cholinergic receptor subtypes in such processes remains elusive. In study IV we investigated the function of muscarinic M4Rs on dopamine D1R expressing neurons and acetylcholinergic neurons, using transgenic mice in various reward-enforced behaviors and in a “waiting”-impulsivity test. Mice lacking M4-receptors from D1-receptor expressing neurons exhibited an escalated reward seeking phenotype towards cocaine and natural reward, in Pavlovian conditioning and an operant self-administration task, respectively. In addition, the M4-D1RCre mice showed impaired waiting impulsivity in the 5-choice-serial-reaction-time-task. On the contrary, mice without M4Rs in acetylcholinergic neurons were unable to learn positive reinforcement to natural reward and cocaine, in an operant runway paradigm and in Pavlovian conditioning.  Immediate early gene expression mirrored the behavioral findings arising from M4R-D1R knockout, as cocaine induced cFos and FosB was significantly increased in the forebrain of M4-D1RCre mice, whereas it remained normal in the M4R-ChatCre mice. Our study illustrates that muscarinic M4Rs on specific neural populations, either cholinergic or D1R-expressing, are pivotal for learning processes related to both natural reward and drugs of abuse, with opposing functionality.

Background: Drug rehabilitation is crucial for drug addicts. As much as drug rehabilitation (rehab) centres are helping in dealing with drug addiction. Some drug addicts may find that some of the drug rehabs do not meet their needs. Therefore, the study explored the experience of caregivers caring for nyaope addicts. Method: This study adopted a qualitative research approach and a case study design. The purposive sampling method was employed to select the sample. The sample comprised six caregivers. The structured interview and open-ended questionnaire were employed to collect data. An interview questionnaire was designed allowing the participants to respond at home and provide feedback. Their responses provided through this process were insufficient, participants were then requested face-to-face interviews and they agreed. Results: One of the main findings in this study was that caregiving affects the caregivers negatively. Caregiving has led to psychological and physical effects amongst the caregivers. Conclusion: A need was identified for support and awareness for the caregivers and rehabilitation centres in South Africa. This might reduce the relapse of substance abuse and help eradicate the number of substance abusers in South Africa. / Psychology / M.A. (Psychology (Research Consultation))

Indiana University-Purdue University Indianapolis (IUPUI) / Methamphetamine (MA) is a widely abused psychostimulant that has been shown to evoke an array of neurobiological abnormalities and cognitive deficits in humans and in rodent models (Marshall & O'Dell, 2012). Alterations in cognitive function after repeated drug use may lead to impaired decision-making, a lack of behavioral control, and ultimately the inability to abstain from drug use. Human studies have shown that alterations in neurobiology resulting from prolonged MA use may lead to a number of cognitive deficits, including impairments in executive function, learning, memory, and impulsivity. These impairments, specifically those that engage the prefrontal cortex (PFC) or hippocampus (HC), may persist or recover based on the duration of abstinence. In rodents, repeated intermittent injections of MA yield protracted changes in neurobiology and behavior, which have been shown to effectively model a number of the biological and cognitive abnormalities observed in addiction. In order to assess the temporal evolution of impaired cognitive function throughout abstinence, sensitization was first induced in rats (7 x 5.0 mg/kg MA over 14 days). MA-treated rats initially exhibited a robust increase in locomotion that transitioned to stereotypy as the induction phase progressed. Then, the effects of MA sensitization on social interaction (SI), temporal order recognition (TOR) and novel object recognition (NOR) was assessed at one-day and 30-days post induction. No differences were observed in SI in either group or after a single injection of MA. However, an acute injection of 5.0 mg/kg of MA 30-minutes prior to testing dramatically reduced SI time. Impairments in TOR and NOR were observed in MA-treated rats after one day of abstinence, and impairments in TOR, but not NOR, were observed on day 30 of abstinence. No differences in TOR and NOR after a single injection of MA or saline were observed. These data establish that after 30 days of abstinence from a sensitizing regimen of MA, the ability to recall the temporal sequence that two stimuli were encountered was impaired and that was not attributable to impaired novelty detection. These data also suggest that at least some of the neurocognitive abnormalities caused by chronic MA administration may normalize after prolonged abstinence, since the ability to detect novelty recovered after 30 days of abstinence. These data provide compelling support that, since MA-sensitization caused temporal deficits in memory, PFC and HC function may be differentially impaired throughout the time course of abstinence.