Neuroleptic drugs are essential in the treatment of schizophrenia and many other psychiatric disorders. These drugs do however cause a wide range of side effects which can be very distressing to patients. In particular the acute neurological side effects of parkinsonism, akathisia and dystonia, which are termed extrapyramidal syndromes, can be a limiting factor in the use of these drugs (Weiden et al 1987). Fort Napier Hospital is a large psychiatric referral hospital and the majority of patients admitted require neuroleptic drug treatment. Extrapyramidal side effects are regularly seen amongst these patients. This study was designed to discover the incidence of parkinsonism, akathisia and dystonia amongst patients treated with neuroleptic drugs and what specific factors were responsible for these side effects. Relevant literature on this topic was reviewed and comparable studies done in America, Europe and South Africa are discussed. The study sample consisted of one hundred patients who were examined regularly over a two week period for signs of parkinsonism, akathisia, or dystonia which were rated quantitatively according to specific rating scales. Patient and drug variables were then analysed to assess what factors were responsible for these side effects. The incidence of drug-induced parkinsonism was 29%, akathisia 35% and dystonia 20%. Combinations of these three syndromes were observed resulting in an overall incidence of 47%. High potency drugs such as haloperidol and trifluoperazine were responsible for a large percentage of all the side effects, while of the low potency drugs, thioridazine produced less side effects than chlorpromazine. Oral drugs combined with intramuscular depot drugs resulted in a high incidence of side effects. The phase of treatment was clinically important with dystonia occurring more often within the first three days of treatment, akathisia within ten days and parkinsonism after ten to fourteen days. Other factors that were studied included the patients age, sex and prior history of neuroleptic-induced neurological side effects. Due to the predominantly young patient population in this study, the mean age of those patients who developed parkinsonism was 26,7 years, akathisia 27,5 years and dystonia 25,8 years. These side effects were seen more commonly in males than in females. Of the 27 patients in this study who had a prior history of neurological side effects, 15 (56%) developed similar side effects following re-exposure to neuroleptic drugs. Conclusions derived from this study include the need for clinicians to select the correct type and dose of neuroleptic for individual patients in order to minimize the development of neurological side effects. Accurate, early diagnosis of side effects by regular examination of patients is necessary for effective patient management. Clinicians should be made more aware of the side effects that can develop with the use of neuroleptic drugs and the effect these side effects have on patients. / Thesis (M.Med)-University of Natal, 1993.

Thesis (Ph.D.) - Carleton University, 2002. / Includes bibliographical references (p. 264-326). Also available in electronic format on the Internet.

Action control arises from the interaction of two anatomically distinct decision-making systems, namely goal-directed and habitual behaviour. Goal-directed behaviour is characterized by the consideration of future choices and respective outcomes whereas habitual responding is driven by stimulus-response associations. Response inhibition is essential for goal-directed behaviour and deficits are shown in impulsivity. We administered an acute clinically relevant dosage of the commonly used serotonin reuptake inhibitor escitalopram to sixty-six healthy volunteers in a double-blind, randomized, placebo-controlled design. We administered a large task battery in order to study the effect of escitalopram in several cognitive functions including response inhibition, learning and affective processing. We found dissociate effects on cognitive aspects possibly mediated by distinct cortico-striatal loops. Acute escitalopram administration had a beneficial effect on action cancellation, one aspect of inhibitory control, without any effect on action restraint or waiting impulsivity. The treatment resulted in impaired performance in a probabilistic reversal-learning task and increased sensitivity to misleading feedback thus leading to maladaptive performance. An extra-dimensional set shift impairment during an attention set shift task and a tendency towards impaired instrumental learning discrimination were also observed in the escitalopram group. Our results are discussed in the context of well-documented effects of the dopaminergic system and suggestions of opponent interaction of serotonin and dopamine.

Thesis (M.A.)--University of North Carolina at Wilmington, 2003. / Includes bibliographical references (leaves : [84]-89).

No description available.

Thesis (M. Sc.)--Carleton University, 2001. / Includes bibliographical references (p. 113-138). Also available in electronic format on the Internet.

The present study attempted to predict the serious side effects of akathisia and parkinsonism on the basis of individualized measurement of changes in visuomotor functioning. The following were the hypotheses for this investigation. 1. A deterioration of visuomotor ability as measured by a modification of Haase and Janssen' s (1965) Handwriting Test will predict which patients undergoing neuroleptic therapy will experience the extrapyramidal symptoms of akathisia and parkinsonism (symptom group) and which will not (no-symptom group). 2. A deterioration of visuomotor ability as measured by the Bender-Gestalt will predict which patients undergoing neuroleptic therapy will experience the extrapyramidal symptoms of akathisia and parkinsonism (symptom group) and which will not (no-symptom group). It was not possible to predict the symptom group as a whole on the basis of the Handwriting Test scores since a t test of the difference was not significant between group means. However, inspection of these scores showed clear deterioration of performance among the patients who experienced parkinsonian reactions as opposed to those who experienced akathisia or who did not experience extrapyramidal symptoms at all. The symptom group was separated into akathisic and parkinsonian groups and compared to the subjects who did not experience extrapyramidal side effects (no-symptom group). A one-way ANOVA showed a nonsignificant difference between the three groups. Similar analysis of the Bender-Gestalt scores failed to support the second hypothesis since no significant difference was found between groups.

Indiana University-Purdue University Indianapolis (IUPUI) / Extrasynaptic GABAA receptors, often identified as those containing both α4 and δ subunits, appear to be a target for the actions of alcohol (ethanol) at relatively low concentrations, perhaps suppressing the activity of GABAergic interneurons which regulate activity in the mesolimbocortical circuit. Pharmacological studies in rodents using the δ-subunit selective agonist Gaboxadol (THIP) have found both promotional and inhibitory effects on alcohol consumption. The goal of this project was to determine the role of extrasynaptic GABAA receptors located in the infralimbic cortex (ILC) in the binge-like alcohol intake of male C57BL/6J (B6) mice. The ILC is of interest due to its demonstrated involvement in stress reactivity and alcohol exposure has been shown to interfere with extinction learning; impairments of which may be related to inflexible behavior (i.e. problematic alcohol consumption). Adult male B6 mice were bilaterally implanted with stainless steel guide cannulae aimed at the ILC and were offered limited access to 20% ethanol or 5% sucrose for 6 days. On day 7, mice were bilaterally injected with 50 or 100 ng THIP (25 or 50 ng per side respectively) or saline vehicle into the ILC. It was found that the highest dose of THIP (100 ng/mouse) increased alcohol intake relative to vehicle controls, although control animals consumed relatively little ethanol following infusion. Furthermore, THIP had no effect on sucrose consumption (p > 0.05), suggesting that the effect of THIP was selective for ethanol consumption. Together, these findings suggest that the mice that consumed ethanol may have been particularly reactive to the microinfusion process relative to animals that consumed sucrose, perhaps because ethanol consumption was not as reinforcing as sucrose consumption. In addition, the observation that THIP effectively prevented the decrease in ethanol intake on day 7 induced by the microinjection process may be related to a role for the ILC in adaptive learning processes, which in turn, promote behavioral flexibility.