Thesis (doctoral)--Uppsala University, 1983. / Includes bibliographical references (p. 26-33).

Because chronic haloperidol-treated rats demonstrate an increased incidence of spontaneous oral activity, while neonatal 6-hydroxydopamine-lesioned rats demonstrate an increased incidence of dopamine agonist-induced oral activity, we studied the influence of haloperidol in 6-hydroxydopamine-lesioned rats. At 3 days after birth rats received 6-hydroxydopamine hydrobromide (200 μg intracerebroventricularly; desipramine pretreatment, 20 mg/kg i.p., 1 h) or vehicle. Two months later haloperidol (1.5 mg/kg per day × 2 days per week, for 4 weeks; then 1.5 mg/kg per day, every day for 10 months) was added to the drinking water. After 15 weeks the level of spontaneous oral activity was stable. At 11 months there were 35.8 ± 4.9 vs. 18.4 ± 2.1 oral movements in 6-hydroxydopamine-lesioned vs. intact rats receiving haloperidol. This effect persisted unabated in lesioned rats for 4 months after haloperidol withdrawal. This stable high frequency of oral dyskinesias is an advantage for studying putative therapeutic drugs for tardive dyskinesia.

Thesis (doctoral)--University of Uppsala, 1984. / Bibliography: p. 33-45.

Thesis (M.S.)--Brock University, 2005. / Includes bibliographical references. Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (M.S.)--Brock University, 2005. / Includes bibliographical references.

Drosophila provide an excellent model organism in which to study cilia as there are only two ciliated cell types; the sensory neurons and sperm cells. The chordotonal neuron is one such ciliated cell and is required for hearing, proprioception and gravitaxis. Mechanical manipulation of the cilium that extends from the neuronal dendrite is required for signal transduction. Chordotonal neuronal differentiation is regulated by a transcription factor cascade. Atonal begins the cascade, which is then continued by RFX and Fd3F for ciliary genes (Cachero et al 2011, Newton et al 2012). Genes expressed in developing chordotonal neurons are downstream of these transcription factors and their characterisation can further elucidate how neuronal differentiation is regulated. Ciliary genes are highly enriched in developing chordotonal cells; uncharacterised genes enriched in these cells can therefore be considered candidate ciliary genes (Cachero et al 2011). A behavioural assay was conducted to identify further genes that could have a role in ciliary formation and function. Candidate genes were identified by combining enrichment data with previous genomic, proteomic and transcriptomic studies of cilia. A climbing assay of RNAi mediated knock down of these genes identified a number of candidates for future work. One gene found to be highly enriched in developing chordotonal neurons is CG11253. CG11253EY10866 P element insertion mutant flies show a mild uncoordinated phenotype in a climbing assay consistent with reduced chordotonal organ function. Male flies are also infertile due to a lack of motile sperm. CG11253 is expressed in motile ciliated cells and is conserved in organisms with motile cilia. CG11253 expression is also regulated by RFX and Fd3F, suggesting that it is involved in cilium motility. This was confirmed by electron microscopy, which showed disruption of axonemal dynein arm localisation in chordotonal cilia and sperm flagella. A CG11253::mVenus fusion protein was found to localise mainly to the cytoplasm and to a lesser extent the cilia of chordotonal neurons. Patients with symptoms consistent with Primary Ciliary Dyskinesia (PCD), a condition caused by cilium immotility, have subsequently been found to have point mutations in ZMYND10, the human homologue of CG11253. The identification of PCD patients with ZMYND10 mutations showed that investigating cilium motility in Drosophila chordotonal neurons could identify novel PCD genes. It was thought that investigating previously uncharacterised targets of Fd3F could identify novel genes involved in cilium motility and thus candidate PCD genes. CG31320 is a gene regulated by RFX and Fd3F and conserved in organisms with motile cilia. RNAi mediated knock down of CG31320 resulted in both a mild uncoordinated phenotype and male infertility due to a lack of motile sperm. Electron microscopy showed a complete loss of axonemal dynein arms in chordotonal neuron cilia. An mVenus fusion protein of CG6971, an inner dynein arm component, was also mislocalised from the cilia in CG3132027 deletion mutant larvae. This shows that CG31320 is required for the appropriate localisation of the axonemal dynein arms and thus cilium motility. This further showed that uncharacterised genes enriched in chordotonal neurons and regulated by Fd3F could be novel ciliary genes required for cilium motility. Our collaborators and Horani et al (2012) showed that the human homologue of CG31320 (HEATR2) is mutated in patients with PCD, further confirming that this method can be used to identify PCD genes. I have identified two factors required for cilium motility. Disruption of the axonemal dynein arms in both cases results in reduced coordination, and lack of fertility due to sperm immotility. Mutations in the human homologues of these genes have been found to result in PCD. This indicates that further PCD genes could be identified from genes enriched in Drosophila chordotonal neurons that are regulated by Fd3F.

The effectiveness of progressive relaxation training in decreasing the severity of neuroleptic-induced tardive dyskinesia (TD) was examined in the current study. Three residents at a county-owned nursing home who had been receiving neuroleptic medications for a number of years to treat severe mental illness participated in this study. A multiple baseline across subjects design was used to evaluate the effect of progressive relaxation training on the participant's orofacial TD symptomatology. The severity of each participant's orofacial TD was observed to improve when the intervention was introduced. Treatment integrity and IOA data that were collected indicate that the intervention was implemented at a high level of fidelity and that data were reliable. Thus, a clear functional relationship was established between progressive relaxation training and severity of orofacial TD in this study. Although the present study was preliminary in nature, the results that were obtained provide a basis upon which to develop a behavioral treatment protocol for managing TD.

Thesis (M.S.)--Brock University, 2005. / Includes bibliographical references. Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (M.S.)--Brock University, 2005. / Includes bibliographical references.

Drug-induced tardive dyskinesia, an irreversible involuntary movement disorder caused by neuroleptic drugs, may reflect cholinergic hypofunction in the corpus striatum. Therapeutic results have been reported in trials of choline and lecithin, nutritional substrates which may enhance cholinergic neurotransmission. Lecithin's effects on dyskinetic symptoms were examined in 50 male patients in a double-blind, placebo-controlled trial. Patients were randomly assigned to treatment or control groups; 31 patients were retained in the analytic cohort. Experimental patients were treated with 60 gm/day lecithin (55% phosphatidyl choline) for 11 days. Symptom frequency was rated from videotapes made at baseline, 3 and 11 days of treatment, and 1 week follow-up.