Date of Award

1968

Degree Type

Dissertation

Degree Name

Doctor of Philosophy in Pharmaceutical Sciences

Specialization

Pharmacy

Department

Pharmacology

First Advisor

John J. DeFeo

Abstract

The effect of guanethidine (1.20 mg/kg, i.p.) or reserpine (0.2 mg/kg, i.p.) has been compared on various indices of pituitary-adrenal stimulation in rats subjected to chronic forced restraint for 24 days. This was accomplished by analyzing the serum corticosterone, the adrenal ascorbic acid (AAA) and various organ weights such as the adrenals, brain and heart. Peripheral and central norepinephrine (NE) was also measured.

Chronically stressed, control rats or those treated with guanethidine demonstrated both behavioral and neurochemical adaptation. Initial excitation associated with restraint was related to changes in NE in the brain and heart. As the experiment progressed, the stressed, guanethidine treated animals showed changes in peripheral NE that were similar to those of the stressed, vehicle-treated animals; whereas, the non-stressed guanethidine- treated animals showed a progressive decline in peripheral NE over the 24 day study. This change in the peripheral NE in the stressed, guanethidine-treated animals was attributed to increased production of NE, perhaps by the adrenals, since low doses of guanethidine do not affect adrenal catecholamines.

Reserpine-treated, stressed animals showed 40% mortality over the 24 day period, thus indicating non-adaptation. This increased mortality was not due to starvation or decreased water intake. It is suggested that non-adaptation in these animals may be due to a chemical sympathectomy, and the animals were unable to respond to severe changes in the environment.

Changes in behavior, in the different groups of animals, were correlated with changes in brain NE. Evidence is also presented indicating that reserpine and guanethidine do not deplete heart NE by the same mechanism(s).

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