Post-traumatic stress disorder (PTSD) is a severe anxiety disorder affecting cognitive function. 1 in 4 individuals exposed to a life-threatening event may develop PTSD, which is characterised by symptoms of hyperarousal, avoidance and intrusions. Although treatment is effective in most cases, the response is far from satisfactory. It is now clear that novel drug treatment and a better understanding of the neurobiology of PTSD are necessary if we are to realise a better response and treatment outcome in these patients. Glutamatergic pathways play an important role in cognition, while recent studies have emphasized a causal role for glutamate in PTSD, and of the potential value of glutamate receptor modulators in treating the disorder. Stress-related elevation in glutamate exerts detrimental effects on cognition, especially via activation of the N-methyl-D-aspartate (NMDA) receptor, and has been implicated in PTSD associated cognitive deficits. Recently, the cr-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor has been found to exert a modulatory action on NMDA receptor function. Ampakines are positive allosteric modulators of the AMPA receptor, and have demonstrated beneficial effects in animal models of learning as well as antidepressant action, and to improve short-term memory in humans. The aims of this study were firstly to study the effects of the ampakine, Org 26576, on spatial memory performance in healthy male Sprague-Dawley rats. Secondly, since PTSD is associated with pronounced deficits in cognition, we studied the ability of Org 26576 to modify stress-evoked spatial memory deficits in rats subjected to single prolonged stress (SPS), a putative animal model of PTSD. In both cases, neuroreceptor studies were performed to determine any relationship between hippocampal and cortical NMDA receptor binding characteristics and effects on spatial memory performance. After exposure of the animals to either normal handling or SPS conditions, spatial memory performance was assessed using a 5 day memory acquisition and consolidation protocol in a modified version of the Morris water maze (MWM). Experimental and control groups both received either saline (1 ml/kg i.p.) or Org 26576 at incremental doses of 1, 3 or 10 mg/kg intraperitoneally twice daily for 12 days. Separate groups of animals were used for the neuroreceptor studies, except that behavioural testing was not performed. 24hrs after drug treatment discontinuation, the animals were sacrificed and frontal cortex and hippocampus removed for NMDA receptor binding analysis. In normal rats, Org 26576 3 mg/kg and 10 mg/kg exerted a short-lasting reduction in escape latency on day 1, but which lost prominence over the subsequent training days. Org 26576 1, 3 and 10 mg/kg, however, significantly improved spatial memory retrieval on day 5. No changes in frontal cortical or hippocampal NMDA receptors were observed. Contrary to expected, rats subjected to SPS failed to express noteworthy deficits in spatial memory as previously described. Treatment of SPS-exposed animals with Org 26576 did not significantly alter spatial learning evident in SPS animals on day 1 of acquisition training, as well as on subsequent training days. Org 26576 1 mg/kg increased spatial memory retrieval compared to the unstressed saline control, but not compared to the SPS group. Org 26576 only at a dose of 1 mg/kg decreased cortical, but not hippocampal NMDA receptor density (Bmax) in SPS animals versus unstressed but not saline treated SPS animals. No changes in receptor affinity (Kd) were noted. Org 26576 therefore improves early initial spatial learning in healthy rats, but exerts a lesser effect on memory consolidation over the remainder of the training period. However, Org 26576 significantly improves retrieval of spatial memory without simultaneous changes in frontal cortical and hippocampal NMDA receptor binding. Org 26576 thus may benefit both short-term and long-term memory processes in normal animals without effects on limbic NMDA receptor binding, and provides a rationale for testing in conditions that present with cognitive disturbances. However, the SPS model failed to engender marked deficits in spatial memory performance; this result ultimately complicated the interpretation of the combined stress-drug treatment studies. Studies in healthy animals therefore conclude that Org 26576 is an effective agent to enhance long-term memory processes and should be investigated further for its possible application in disorders of cognition. Although the value of Org 26576 in an animal model of PTSD were inconclusive, further studies in SPS and other PTSD models, as well as models of relevance for schizophrenia, Alzheimer's disease and depression, are encouraged. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2009.

Post-traumatic stress disorder (PTSD) is a severe anxiety disorder affecting cognitive function. 1 in 4 individuals exposed to a life-threatening event may develop PTSD, which is characterised by symptoms of hyperarousal, avoidance and intrusions. Although treatment is effective in most cases, the response is far from satisfactory. It is now clear that novel drug treatment and a better understanding of the neurobiology of PTSD are necessary if we are to realise a better response and treatment outcome in these patients. Glutamatergic pathways play an important role in cognition, while recent studies have emphasized a causal role for glutamate in PTSD, and of the potential value of glutamate receptor modulators in treating the disorder. Stress-related elevation in glutamate exerts detrimental effects on cognition, especially via activation of the N-methyl-D-aspartate (NMDA) receptor, and has been implicated in PTSD associated cognitive deficits. Recently, the cr-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor has been found to exert a modulatory action on NMDA receptor function. Ampakines are positive allosteric modulators of the AMPA receptor, and have demonstrated beneficial effects in animal models of learning as well as antidepressant action, and to improve short-term memory in humans. The aims of this study were firstly to study the effects of the ampakine, Org 26576, on spatial memory performance in healthy male Sprague-Dawley rats. Secondly, since PTSD is associated with pronounced deficits in cognition, we studied the ability of Org 26576 to modify stress-evoked spatial memory deficits in rats subjected to single prolonged stress (SPS), a putative animal model of PTSD. In both cases, neuroreceptor studies were performed to determine any relationship between hippocampal and cortical NMDA receptor binding characteristics and effects on spatial memory performance. After exposure of the animals to either normal handling or SPS conditions, spatial memory performance was assessed using a 5 day memory acquisition and consolidation protocol in a modified version of the Morris water maze (MWM). Experimental and control groups both received either saline (1 ml/kg i.p.) or Org 26576 at incremental doses of 1, 3 or 10 mg/kg intraperitoneally twice daily for 12 days. Separate groups of animals were used for the neuroreceptor studies, except that behavioural testing was not performed. 24hrs after drug treatment discontinuation, the animals were sacrificed and frontal cortex and hippocampus removed for NMDA receptor binding analysis. In normal rats, Org 26576 3 mg/kg and 10 mg/kg exerted a short-lasting reduction in escape latency on day 1, but which lost prominence over the subsequent training days. Org 26576 1, 3 and 10 mg/kg, however, significantly improved spatial memory retrieval on day 5. No changes in frontal cortical or hippocampal NMDA receptors were observed. Contrary to expected, rats subjected to SPS failed to express noteworthy deficits in spatial memory as previously described. Treatment of SPS-exposed animals with Org 26576 did not significantly alter spatial learning evident in SPS animals on day 1 of acquisition training, as well as on subsequent training days. Org 26576 1 mg/kg increased spatial memory retrieval compared to the unstressed saline control, but not compared to the SPS group. Org 26576 only at a dose of 1 mg/kg decreased cortical, but not hippocampal NMDA receptor density (Bmax) in SPS animals versus unstressed but not saline treated SPS animals. No changes in receptor affinity (Kd) were noted. Org 26576 therefore improves early initial spatial learning in healthy rats, but exerts a lesser effect on memory consolidation over the remainder of the training period. However, Org 26576 significantly improves retrieval of spatial memory without simultaneous changes in frontal cortical and hippocampal NMDA receptor binding. Org 26576 thus may benefit both short-term and long-term memory processes in normal animals without effects on limbic NMDA receptor binding, and provides a rationale for testing in conditions that present with cognitive disturbances. However, the SPS model failed to engender marked deficits in spatial memory performance; this result ultimately complicated the interpretation of the combined stress-drug treatment studies. Studies in healthy animals therefore conclude that Org 26576 is an effective agent to enhance long-term memory processes and should be investigated further for its possible application in disorders of cognition. Although the value of Org 26576 in an animal model of PTSD were inconclusive, further studies in SPS and other PTSD models, as well as models of relevance for schizophrenia, Alzheimer's disease and depression, are encouraged. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2009.

My dissertation, Pen and Printing-Block: William Morris and the Resurrection of Medieval Paratextuality, considers William Morris’s influence on the rise of paratextual awareness, his negotiation strategies for Victorian England’s social identity, and his rhetorical construction of an idealized past through textual artifacts. The effect of Morris’s growing social awareness on his transition from illumination to print is reframed by considering his calligraphy as paratextual experiments, based on medieval examples, in combining graphic and discursive meanings with rhetorical and social dimensions. The varied and less ambitious agendas of those printers who followed Morris’s Kelmscott Press, however, limited Morris’s legacy in the book arts. The full significance of his illuminations’ meaningful interplay between text and image, and the social intent of these innovations applications in print, has received little critical attention. The opening chapter frames Morris’s visual work in light of his philosophies and introduces the major concerns of material art, the role of history, the limits of language, and the question of meaningful labour. The second chapter surveys select predecessors of Morris’s developing conception of the Gothic, the significance of architecture as its defining form, and the irreplaceability of the physical past. The third chapter considers the role of the illuminated manuscript in Pre-Raphaelite art, tracing Morris’s calligraphic experiments chronologically while identifying medieval inspirations and examining his artistic development. These experiments led to his final collaborative manuscript, the illuminated Æneid which is the fourth chapter’s focus. The sophistication of its paratextual elements is discussed in light of its unique physicality and limitations. The fifth chapter asserts the Kelmscott Press’s role in balancing craftsmanship and aesthetic paratextual strategies with reproducible models. The Kelmscott Chaucer is the culmination of these strategies, and it is compared to the visual rhetoric of its predecessors. The final chapter compares the philosophies and calligraphic elements of major private presses that followed Kelmscott’s legacy. This evolution of aesthetic, social, and practical considerations is also identified in the work of selected Canadian printers, and a final note considers the implications of the rise of immaterial digital text (radiant textuality) for the continuation of material paratextuality’s role in the future.

Many studies have suggested a relationship between sex steroids and negative mental and mood changes in women. Allopregnanolone, a potent endogenous ligand of the GABA-A receptor and a metabolite of progesterone, is one of the most accused neuroactive steroids. Variations in the levels of neuroactive steroids that influence the activity of the GABA-A receptor cause a vulnerability to mental and emotional pathology. In women, there are physiological conditions in which allopregnanolone production increases acutely (e.g. stress) or chronically (e.g. menstrual cycle, pregnancy), thus exposing the GABA-A receptor to high allopregnanolone concentrations. In such conditions, tolerance to allopregnanolone probably develops. We have evaluated the 3β-hydroxy pregnane steroid UC1011 as a functional antagonist to allopregnanolone-induced negative effects in rats. In vivo, we used the Morris Water Maze (MWM) test of learning and, in vitro, we studied chloride ion uptake into cortical and hippocampal membrane preparations. The steroid UC1011 reduces the allopregnanolone-induced learning impairment in the MWM and the increase in chloride ion uptake induced by allopregnanolone. To detect whether chronic tolerance develops to an allopregnanolone-induced condition, male rats were pretreated with allopregnanolone injections for three or seven days. These rats were then tested in the Morris Water Maze for five days and compared with relevant controls. Rats with seven days’ allopregnanolone pretreatment experienced improved performance compared with the acutely allopregnanolone-exposed group, reflecting chronic tolerance development. To study the GABA-A receptor changes in acute allopregnanolone tolerance, we used the silent second (SS) anaesthesia threshold method. At acute tolerance, 90 minutes of anaesthesia, the abundance of the GABA-A receptor α4 subunit and the expression of the α4 subunit mRNA in the thalamus ventral-posteriomedial (VPM) nucleus were reduced. There was also a significant negative correlation between the increase in the allopregnanolone dose needed to maintain anaesthesia and the α4 mRNA in the VPM nucleus. We also investigated whether allopregnanolone tolerance was still present one or two days after the end of the anaesthesia-induced acute tolerance. Tolerance persisted to one day, but not two days, after the treatment and the α4 subunit mRNA expression in the VPM nucleus was negatively related to the allopregnanolone doses needed after one day. In conclusion, the current thesis shows that the substance UC1011 can reduce the allopregnanolone-induced negative effects in the water maze test. Chronic allopregnanolone tolerance can develop to the effects of allopregnanolone. Allopregnanolone tolerance persists one day after the induction of acute allopregnanolone tolerance. The GABA-A receptor α4 subunit in the thalamus might be involved in the development and persistence of acute tolerance to allopregnanolone.

Taking my own personal history as a starting point this paper will look at how we inherit culture and in turn shape it through the stories and objects that drive its formation. This extends into how these objects proliferate within our culture and the way in which the passing of History impacts on the way we view them and as a consequence ourselves as individuals and as a group. Identity is then passed on through generations through the act of storytelling, and this process is integral to this research paper. This is also a personal journey, taking place in varying sites, from a rusting car hulk in a back yard in North Canterbury, to a University in Wellington and another rusted car, which has gone through a strange restoration. The Morris Minor has been embraced as a narcissistic object that I have chosen to double in order to explore my individual and wider national cultural history and identity. One of the key themes of this inherited identity is largely based around Nostalgia for an ideal past. This ideal is a fiction, a layering of intended futures as well as a selective past. This works in the same way as the modern artistic preoccupation with gothic histories, but instead of a positive ideal we have the creation of a basement of horrors that lurks beneath the surface. Be it positivist idealism or Gothic inversion, one way of focusing on the way these fictions differ markedly from the reality of the objects existence, is to show the artifice of the stories told by enhancing the components of the story that are already exaggerated, for the Morris Minor this means getting as far away from its existence as a rusting hulk in the backyard as possible. The longing for a past that may or may not exist, is less important as existing in reality but instead for what these fictions supply in their retelling. The concept of the Uncanny is integral to this retelling of memory, in that through a memories reanimation it can only approximate the original event leaving gaps for circumspection and invention. This retelling necessitates a reorientation in the relationship between the teller of the tale and the listener and between the viewer and the object viewed. The research culminates in the alteration of a Morris Minor to appear as one continuous surface. The intention of which is to engage with the differing versions of the objects past through taking an active part in its reconstruction as artwork with the aim of reassessment not only of my individual approach to the object but also the viewers.

Taking my own personal history as a starting point this paper will look at how we inherit culture and in turn shape it through the stories and objects that drive its formation. This extends into how these objects proliferate within our culture and the way in which the passing of History impacts on the way we view them and as a consequence ourselves as individuals and as a group. Identity is then passed on through generations through the act of storytelling, and this process is integral to this research paper. This is also a personal journey, taking place in varying sites, from a rusting car hulk in a back yard in North Canterbury, to a University in Wellington and another rusted car, which has gone through a strange restoration. The Morris Minor has been embraced as a narcissistic object that I have chosen to double in order to explore my individual and wider national cultural history and identity. One of the key themes of this inherited identity is largely based around Nostalgia for an ideal past. This ideal is a fiction, a layering of intended futures as well as a selective past. This works in the same way as the modern artistic preoccupation with gothic histories, but instead of a positive ideal we have the creation of a basement of horrors that lurks beneath the surface. Be it positivist idealism or Gothic inversion, one way of focusing on the way these fictions differ markedly from the reality of the objects existence, is to show the artifice of the stories told by enhancing the components of the story that are already exaggerated, for the Morris Minor this means getting as far away from its existence as a rusting hulk in the backyard as possible. The longing for a past that may or may not exist, is less important as existing in reality but instead for what these fictions supply in their retelling. The concept of the Uncanny is integral to this retelling of memory, in that through a memories reanimation it can only approximate the original event leaving gaps for circumspection and invention. This retelling necessitates a reorientation in the relationship between the teller of the tale and the listener and between the viewer and the object viewed. The research culminates in the alteration of a Morris Minor to appear as one continuous surface. The intention of which is to engage with the differing versions of the objects past through taking an active part in its reconstruction as artwork with the aim of reassessment not only of my individual approach to the object but also the viewers.

Taking my own personal history as a starting point this paper will look at how we inherit culture and in turn shape it through the stories and objects that drive its formation. This extends into how these objects proliferate within our culture and the way in which the passing of History impacts on the way we view them and as a consequence ourselves as individuals and as a group. Identity is then passed on through generations through the act of storytelling, and this process is integral to this research paper. This is also a personal journey, taking place in varying sites, from a rusting car hulk in a back yard in North Canterbury, to a University in Wellington and another rusted car, which has gone through a strange restoration. The Morris Minor has been embraced as a narcissistic object that I have chosen to double in order to explore my individual and wider national cultural history and identity. One of the key themes of this inherited identity is largely based around Nostalgia for an ideal past. This ideal is a fiction, a layering of intended futures as well as a selective past. This works in the same way as the modern artistic preoccupation with gothic histories, but instead of a positive ideal we have the creation of a basement of horrors that lurks beneath the surface. Be it positivist idealism or Gothic inversion, one way of focusing on the way these fictions differ markedly from the reality of the objects existence, is to show the artifice of the stories told by enhancing the components of the story that are already exaggerated, for the Morris Minor this means getting as far away from its existence as a rusting hulk in the backyard as possible. The longing for a past that may or may not exist, is less important as existing in reality but instead for what these fictions supply in their retelling. The concept of the Uncanny is integral to this retelling of memory, in that through a memories reanimation it can only approximate the original event leaving gaps for circumspection and invention. This retelling necessitates a reorientation in the relationship between the teller of the tale and the listener and between the viewer and the object viewed. The research culminates in the alteration of a Morris Minor to appear as one continuous surface. The intention of which is to engage with the differing versions of the objects past through taking an active part in its reconstruction as artwork with the aim of reassessment not only of my individual approach to the object but also the viewers.

Taking my own personal history as a starting point this paper will look at how we inherit culture and in turn shape it through the stories and objects that drive its formation. This extends into how these objects proliferate within our culture and the way in which the passing of History impacts on the way we view them and as a consequence ourselves as individuals and as a group. Identity is then passed on through generations through the act of storytelling, and this process is integral to this research paper. This is also a personal journey, taking place in varying sites, from a rusting car hulk in a back yard in North Canterbury, to a University in Wellington and another rusted car, which has gone through a strange restoration. The Morris Minor has been embraced as a narcissistic object that I have chosen to double in order to explore my individual and wider national cultural history and identity. One of the key themes of this inherited identity is largely based around Nostalgia for an ideal past. This ideal is a fiction, a layering of intended futures as well as a selective past. This works in the same way as the modern artistic preoccupation with gothic histories, but instead of a positive ideal we have the creation of a basement of horrors that lurks beneath the surface. Be it positivist idealism or Gothic inversion, one way of focusing on the way these fictions differ markedly from the reality of the objects existence, is to show the artifice of the stories told by enhancing the components of the story that are already exaggerated, for the Morris Minor this means getting as far away from its existence as a rusting hulk in the backyard as possible. The longing for a past that may or may not exist, is less important as existing in reality but instead for what these fictions supply in their retelling. The concept of the Uncanny is integral to this retelling of memory, in that through a memories reanimation it can only approximate the original event leaving gaps for circumspection and invention. This retelling necessitates a reorientation in the relationship between the teller of the tale and the listener and between the viewer and the object viewed. The research culminates in the alteration of a Morris Minor to appear as one continuous surface. The intention of which is to engage with the differing versions of the objects past through taking an active part in its reconstruction as artwork with the aim of reassessment not only of my individual approach to the object but also the viewers.

Taking my own personal history as a starting point this paper will look at how we inherit culture and in turn shape it through the stories and objects that drive its formation. This extends into how these objects proliferate within our culture and the way in which the passing of History impacts on the way we view them and as a consequence ourselves as individuals and as a group. Identity is then passed on through generations through the act of storytelling, and this process is integral to this research paper. This is also a personal journey, taking place in varying sites, from a rusting car hulk in a back yard in North Canterbury, to a University in Wellington and another rusted car, which has gone through a strange restoration. The Morris Minor has been embraced as a narcissistic object that I have chosen to double in order to explore my individual and wider national cultural history and identity. One of the key themes of this inherited identity is largely based around Nostalgia for an ideal past. This ideal is a fiction, a layering of intended futures as well as a selective past. This works in the same way as the modern artistic preoccupation with gothic histories, but instead of a positive ideal we have the creation of a basement of horrors that lurks beneath the surface. Be it positivist idealism or Gothic inversion, one way of focusing on the way these fictions differ markedly from the reality of the objects existence, is to show the artifice of the stories told by enhancing the components of the story that are already exaggerated, for the Morris Minor this means getting as far away from its existence as a rusting hulk in the backyard as possible. The longing for a past that may or may not exist, is less important as existing in reality but instead for what these fictions supply in their retelling. The concept of the Uncanny is integral to this retelling of memory, in that through a memories reanimation it can only approximate the original event leaving gaps for circumspection and invention. This retelling necessitates a reorientation in the relationship between the teller of the tale and the listener and between the viewer and the object viewed. The research culminates in the alteration of a Morris Minor to appear as one continuous surface. The intention of which is to engage with the differing versions of the objects past through taking an active part in its reconstruction as artwork with the aim of reassessment not only of my individual approach to the object but also the viewers.

Taking my own personal history as a starting point this paper will look at how we inherit culture and in turn shape it through the stories and objects that drive its formation. This extends into how these objects proliferate within our culture and the way in which the passing of History impacts on the way we view them and as a consequence ourselves as individuals and as a group. Identity is then passed on through generations through the act of storytelling, and this process is integral to this research paper. This is also a personal journey, taking place in varying sites, from a rusting car hulk in a back yard in North Canterbury, to a University in Wellington and another rusted car, which has gone through a strange restoration. The Morris Minor has been embraced as a narcissistic object that I have chosen to double in order to explore my individual and wider national cultural history and identity. One of the key themes of this inherited identity is largely based around Nostalgia for an ideal past. This ideal is a fiction, a layering of intended futures as well as a selective past. This works in the same way as the modern artistic preoccupation with gothic histories, but instead of a positive ideal we have the creation of a basement of horrors that lurks beneath the surface. Be it positivist idealism or Gothic inversion, one way of focusing on the way these fictions differ markedly from the reality of the objects existence, is to show the artifice of the stories told by enhancing the components of the story that are already exaggerated, for the Morris Minor this means getting as far away from its existence as a rusting hulk in the backyard as possible. The longing for a past that may or may not exist, is less important as existing in reality but instead for what these fictions supply in their retelling. The concept of the Uncanny is integral to this retelling of memory, in that through a memories reanimation it can only approximate the original event leaving gaps for circumspection and invention. This retelling necessitates a reorientation in the relationship between the teller of the tale and the listener and between the viewer and the object viewed. The research culminates in the alteration of a Morris Minor to appear as one continuous surface. The intention of which is to engage with the differing versions of the objects past through taking an active part in its reconstruction as artwork with the aim of reassessment not only of my individual approach to the object but also the viewers.