Date Thesis Awarded

5-2015

Document Type

Honors Thesis

Degree Name

Bachelors of Science (BS)

Department

Neuroscience

Advisor

John D. Griffin

Committee Member

Randolph A. Coleman

Committee Member

Beverly T. Sher

Abstract

Introduction:

Recent studies have identified a link between gabapentin (GP) treatment and a decrease in the incidence and severity of hot flashes (HFs) among predisposed individuals. The current research is focused on determining whether GP acts directly on neurons within the preoptic anterior hypothalamus in order to cause a change in the body’s thermoregulatory set point and prevent HFs. Chapter one will review current literature, beginning with a discussion of how the human body maintains and regulates its set point temperature with a focus on thermoregulatory neurons of the preoptic anterior hypothalamus (POAH). Hot flashes and the suggested mechanisms by which hypothalamic neurons might modulate them will then be discussed. Next, GP and its potential mechanisms for action will be presented. We hypothesized that treatment with GP would decrease the firing rate of warm sensitive cells as well as temperature insensitive cells in the POAH, which would lead to an increase in set core body temperature based on the current model of neural thermoregulation.

Methods:

Coronal slices of the hypothalamus and surrounding brain areas of adult male Sprague-Dawley rats were prepared and recordings were made on single units. Neurons were classified as either warm sensitive or temperature insensitive and then treated with 10uM GP for ten minutes and then washed for ten minutes with artificial cerebrospinal fluid (aCSF), during which time their firing rates were recorded.

Results:

In response to GP, warm sensitive neurons decreased in their firing rate overall, while most temperature insensitive neurons did not change their firing rate. Twelve temperature insensitive neurons, localized in the periventricular and paraventricular nuclei, increased their firing rate in response to GP.

Conclusions:

The changes in firing rate induced by GP would result in a positive shift in set point (hyperthermia) according to the current model of neural thermoregulation. This hyperthermic shift may contribute to a widened thermoneutral zone in individuals who commonly suffer from HFs and therefore a decrease in HF incidence and/or duration.

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