Holt, Jonathon (2001) A behavioural and electrophysiological study of factors involved in the relationship between stress and alcohol dependence. Doctoral thesis, Durham University.
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.
|Item Type:||Thesis (Doctoral)|
|Award:||Doctor of Philosophy|
|Copyright:||Copyright of this thesis is held by the author|
|Deposited On:||26 Jun 2012 15:23|