Alcohol dependence causes disruption to both work and family life and the associated costs are £150+ million in the UK alone. Stressful life events play a role in initiation of uncontrolled (dependent) drinking and can precipitate relapse to high ethanol consumption after treatment / abstinence. The primary neurological substrate for ethanol reward is the mesolimbic dopamine system of the medial forebrain bundle. Activation of the hypothalamopituitaryadrenal axis (the hormonal response to many stresssors) plays a role in the control of ethanol consumption and relapse, and modulation of neuronal activity by chronic calcium channel blockade decreases ethanol intake, tolerance and withdrawal. The stress system and calcium channel blockade both affect the dopaminergic reward pathways. Hypothesis: Stress and the stress hormone, corticosterone, play a crucial role in the modulation of ethanol consumption and the long term changes resulting from chronic ethanol intake. This hypothesis was tested by investigating the effects of:• social status and calcium channel blockade on chronic ethanol intake (free choice 5, 10, 20% ethanol and water) of group housed rats.• social stress from defeat by an aggressive resident on ethanol preference of low ethanol preference C57 mice.• 6 days abstinence from chronic ethanol intake (liquid diet) on NMDA-stimulated firing of dopaminergic, ventral tegmental area, cells and the role of corticosterone in modulation of this response to NMDA. The main findings from these studies indicate that, while the social stress of group housing under laboratory conditions may be insufficient to elevate ethanol intake, repeated defeat significantly increases ethanol intake. However, neither chronic ethanol consumption nor corticosterone seemd to have any effect on NMDA-stimulated dopamine cell firing. These results indicate a significant role for social stress in the modulation of ethanol intake but possibly not via the action of corticosterone on NMDA-stimulation of the mesolimbic dopamine system.

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The aim of the present investigation was to obtain more information as to the relation between constitution (extended in the sense of configuration in certain instances) and anti-malarial activity in the acridine series and to prepare derivatives of other ring systems, which had not previously been tested for antimalarial activity. Two bases which may resemble 2-amino-5-diethylamino-pentane in configuration were considered for condensations with 5-chloroacridines. The first, o-aminobenzyldiethylamine (I), was prepared by reduction of the nitro compound, obtained by the condensation of o-nitrobenzyl chloride with die thylamine. Four syntheses of the second base, 2-aminocyclohexyldiethylamine (II), were attempted but all were unsuccessful [diagram]. A third base, (3-diethylaminoethylamine, was prepared by the reduction of diethylamino-acetonitrile. 5-Chloroacridine (III) and 2:5-dichlero-7-methoxyacridine (IV) were prepared from the corresponding diphenylamine-2-carboxylio acids and 1:5-dichlero-9-methylacrldine (V) from the corresponding acridone.

Monodansylcadavarine (MDC) was used to synthesise a fluorescent derivative of cyclosporin A and the product of the reaction was isolated by preparative thin layer chromatography (TLC) and purified by high performance liquid chromatography (HPLC). The fluorescent derivative was shown to bind with a polyclonal antibody to cyclosporin A by submitting the derivative for analysis by cyclosporin radioimmunoassay (RIA). However this derivative did not bind with a monoclonal antibody used in a RIA specific for the parent compound. To achieve this fluorescent derivatives were synthesised using cyclosporin-C-hemisuccinate as the staring material with MDC, 4-bromomethyl-7-methoxycoumarin (BMMC), 4-bromomethyl-6,7-dimethoxycoumarin (BMDC) and tetramethyl rhodaminecadavarine (TRC) as the labels. All derivatives were isolated and purified by TLC and HPLC and shown to have antibody binding in the parent compound specific RIA. The fluorescent properties of the derivatives were investigated and the most promising, BMMC and TRC used in the immunoassay development.