Vasopressin, or antidiurectic hormone, has long been known to have peripheral antidiuretic and vasoconstrictor properties. However, more recently a body of research has shown that vasopressin (AVP) affects central nervous system functions by to influencing memory processes. In light of the growing evidence for the role of vasopressin (AVP) in memory, my dissertation research was designed to test the hypothesis that AVP acts as a neuromodulator in the CNS. To test this hypothesis criteria used to establish neurotransmitter status was applied to AVP. Thus, a series of experiments were carried out to investigate (1) AVP brain levels; (2) release of AVP in the CNS; (3) existence of specific AVP binding sites in brain and finally, (4) existence of AVP metabolite peptide, AVP (4-9), binding sites in brain. Results of these experiments indicate that AVP meets some of the criteria for neuromodulator status in the CNS. The detection of AVP in brain, elucidation of the modulatory influence of a CNS depressant upon the content and release of AVP in brain, demonstration and characterization of the regional distribution for putative AVP receptors in brain along with binding sites for a metabolite peptide of AVP, all suggest that AVP acts through receptors within the CNS to influence memory processes.

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Thesis (M. Sc.)--Carleton University, 1996. / Also available in electronic format on the Internet.

Thesis (Ph. D.)--University of California, San Diego, and San Diego State University, 1998. / Vita. Includes bibliographical references (leaves 96-113).

Thesis (Ph. D.)--Carleton University, 2003. / Includes bibliographical references (p. 187-221). Also available in electronic format on the Internet.

Thesis (M.A.) - Carleton University, 2005. / Includes bibliographical references (p. 125-130). Also available in electronic format on the Internet.

It is well established that chronic treatment with neuroleptic agents which selectively block dopamine (DA) receptors in the brain leads to the development of DA receptor supersensitivity. However comparing the degree and duration of the changes in receptor sensitivity obtained by different investigators has been extremely difficult, because of the numerous differences that exist in individual methods of producing and examining DA receptor supersensitivity. By examining the DA receptor supersensitivity that ensues following chronic treatment with different doses and durations of pimozide, at various intervals after withdrawal from treatment, the overall parametric changes can be more directly compared. To measure the changes in DA receptor sensitivity following chronic pimozide treatment, both behavioral (d.-amphetamine-induced locomotor activity; apomorphine-induced stereotypy) and biochemical (DA receptor binding assay) techniques were utilized. With increasing doses of chronic pimozide treatment, the degree and duration of the resulting DA receptor supersensitivity increased as measured both behaviorally and biochemically. Similarily, the longer durations of chronic pimozide treatment had a greater effect on the degree and duration of the increased DA receptor sensitivity than did the shorter durations of treatment. Correlations were found between the biochemical and behavioral results both between groups of animals treated chronically with different doses and durations of pimozide and within individual groups of animals. In addition, the changes in receptor sensitivity following chronic pimozide treatment was due to an increase in the number of DA receptors with no change in the affinity of these receptors to DA. These results following chronic treatment with neuroleptics demonstrate that the behavioral supersensitivity observed in animals in response to either the direct DA agonist apomorphine or the indirect DA agonist d-amphetamine, may be a result of an increased number of DA receptors. Finally, the supersensitive DA receptors that develop as a result of chronic treatment with neuroleptics are discussed with regard to their possible relevance as an animal model of the iatrogenic disease, tardive dyskinesia, observed clinically in schizophrenic patients withdrawn from neuroleptic therapy. / Medicine, Faculty of / Graduate