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Title: Reward mechanisms, depression and drug dependence : psychobiological and developmental mechanisms
Author: Statham, A. J.
Awarding Body: University of Wales Swansea
Current Institution: Swansea University
Date of Award: 1998
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Exposing rodents to a chronic regime of mild stressors (CMS) has been shown to produce enduring decreases in the consumption of palatable weak (1%) sucrose solution. This effect is thought to be analogous to the decreases in reward sensitivity observed in patients suffering from depression. It has been argued that this CMS model represents the most realistic model of depression. Chronic mild stress failed to produce any enduring reductions in sucrose intake, in either inbred or outbred Lister hooded male rats, in three studies. It was hypothesised that early abberant mother-infant interactions would facilitate the appearance of CMS-induced deficits. However, CMS failed to reduce sucrose consumption in either male (inbred Lister hooded) or female (inbred and outbred Lister hooded) rats which had undergone a regime of repeated maternal separation (RMS), or in the respective control rates. These findings add to the growing number of studies challenging the central status of CMS as a valid and reliable animal model of depression. Furthermore, these findings provide compelling evidence in favour of re-evaluating our approach to the study of chronic stress in this country and, furthermore, its contribution to the aetiology of depression. The RMS regime enhanced the locomotor activating effects of a low dose of d-amphetamine. Subsequent studies revealed that 24-hr maternal separation (at postnatal day 3) enhanced and reduced the locomotor activating effects of cocaine in females and males, respectively. These findings are potentially interesting with regard to the study of individual differences in the propensity to drug abuse. However, methodological difficulties impeded the full replication of these findings. The corticosterone synthesis inhibitor metyrapone produced a massive potentiation of the behavioural activating effects of d-amphetamine. This effect was probably the result of metyrapone-induced inhibition of cytochrome P450 2D1, an enzyme involved in the metabolism of d-amphetamine. This finding has potential serious implications for the current clinical use of metyrapone.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available