An Investigation into dopamine function in bipolar and unipolar primary affective disorders measuring prolactin when challenged by chlorpromazine and L-Dihydroxyphenylalanine.
Hart, George Allan Desmond.
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This work is the result of an investigation into aspects of prolactin and dopamine in primary affective disorders. It is introduced by a discussion on the need for obtaining good scientific data on the organic and psychosocial aspects of psychiatric illness, and in particular, primary affective disorders. A short perspective of the history of depressive illness preceeds the review of relevant scientific literature on primary affective disorder. The literature survey covers aspects which indicate organic causal factors as well as viewing numerous organic studies which are thought to be relevant to this investigation. The role of dopamine in motor behaviour is considered in some detail. Psychopharmacological evidence that the mesolimbic and nigrostriatal dopaminergic systems are involved in motor regulation is reviewed. The role of dopamine receptors in motor behaviour is important to the conceptual framework of this thesis. Dopamine D 2 and D 1 receptors are considered and the opposing roles of these receptors is thought to be significant. Drugs affecting manic and depressive phases of primary affective disorders are reviewed. Emphasis is placed on dopaminergic aspects of various drugs in primary affective disorders as with pimozide as an antimanic agent, and nomifensine as an antidepressant. The possible role of noradrenaline in learning and mood regulation and in the dialogue with dopamine is looked at from an experimental and clinical point of view. Dopaminergic control of prolactin is reviewed and in particular the nature of the D4 receptor. The fact that these receptors which are on the pituitary mammotrophs have similarities to the D2 receptors is relevant. Thus considerable commonality exists between the dopaminergic regulation of motor behaviour and regulation of prolactin. Prolactin is used as an index of dopamine function in patients with primary affective disorders. Motor behaviour is strongly influenced by affective disorders.The central theme of the study itself was to indirectly evaluate dopamine function in primary affective disorder by measuring prolactin levels. As strong tonic inhibition is exerted by dopamine on prolactin, a series of challenges to the dopamine system was decided upon in order to generate a number of serum prolactin values. A dopamine agonist L-dihydroxyphenylalanine (indirect) and an antagonist, chlorpromazine, were used to stress the system mildly. The procedure was carried out under standard conditions both in the illness phase and upon significant recovery. Both these investigations were conducted in a drug-free state. The data generated was subjected to statistical analysis. The results of the analysis suggests that prolactin levels are low in depressed patients, and increase upon recovery, while manic patients have elevated levels which decrease with recovery. The pattern of the curves obtained from the challenge procedure suggests a possible supersensitivity of dopamine receptors in the manic patients. Blunting of responses of depressed patients remains a possibility but a study against normal controls is required to further assess this aspect. Evidence is therefore found for altered prolactin levels in illness phases of primary affective disorders. This is thought to be due to an abnormality in the dopamine regulation of prolactin. A discussion on the possible mechanisms and significance of these changes involves Beta-endorphin in an attempt to tie motor changes to mood regulation. Shortcomings of the study and future implications and developments are considered.