Graduation Year

2004

Document Type

Dissertation

Degree

Ph.D.

Degree Granting Department

Psychology

Major Professor

David M. Diamond.

Keywords

Adrenalectomy, Hippocampus, NMDA, Radial-arm water maze, Corticosterone

Abstract

Stress has been shown to influence learning and memory in humans and rats (Diamond et al, 1996; Diamond et al, 1999; Krugers et al, 1997; Kirschbaum et al, 1996; Lupien et al, 1997). The hippocampus and is an area of the brain involved in memory function in humans and rats (Kirschbaum et al, 1996; Lupien et al, 1997) and is highly susceptible to stress (Diamond et al, 1990). Research has indicated that a number of stressors such as exposure to a predator (Diamond et al, 1999) can lead to stress effects. Recently efforts have been made to counteract the effects of stress on brain function and related behavioral performance. The antidepressant drug tianeptine has been used in this setting.

Little is known about tianeptine's role in blocking stress effects on behavior and memory performance with regard to interactions with stress hormones, such as corticosterone. Here a set of experiments delineates the role of corticosterone and its link to stress effects on memory as well as an investigation into the actions of tianeptine and ADX in the blockade of stress effects on memory. First, I examined the effects of tianeptine on multi-day RAWM working memory training and a novel one-day learning and memory training task. Second, the effects of propranolol, an anti-anxiety medication, were tested with regard to the alleviation of stress effects on memory, allowing for a comparison between two anti-anxiety drugs, tianeptine and propranolol. Third, adrenalectomy (ADX) and the resultant depletion of adrenal hormones were examined in connection with learning and memory in the one-day learning task. Fourth, the effects and interactions of tianeptine and ADX were examined to see if tianeptine can exert its effects in the absence of adrenal hormones. Tianeptine blocked stress-induced memory errors in two different tasks and under ADX conditions. All effects were independent of corticosterone levels. In contrast, propranolol was ineffective in blocking stress-induced memory changes. The current data may prove useful in the development of antidepressant drugs and further the study of the mechanisms by which stress affects memory.

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