Mentor: Dr. Earl Thomas
The anti-anxiety, or anxiolytic properties of the drug chlordiazepoxide (CDP), marketed commercially as Librium, have been fully established. The effect of this drug has been studied in rats conditioned to fear certain stimuli, such as tones, which are paired with a shock in order to teach the animal to fear them. When the animal is fearful, the neurons in a structure in the brain called the amygdala increase their rate of firing. This amygdala excitation results behaviorally in signs of fear, such as freezing, increased grooming behaviors, and scanning the environment for dangers. In a sense, the firing of the amygdala IS fear. In conditioned animals, the conditioned stimulus, the tone, creates fear and therefore increased amygdal firing.
CDP, when given to these conditioned rats, decreases amygdal firing upon hearing the tone. That is, the animal is less fearful of the shock to come when they have been dosed with CDP. In addition to directly affecting the amygdala, CDP seems to affect peripheral areas as well. These areas, including the lateral septum and the medial prefrontal area are involved in the balancing of fear responses. Both areas seem to have a reciprocal relationship with the amygdala- when the amygdala increases in firing rate, these other areas decrease in rate, and vice versa. This effect has only been tested when the animal is fearful, anticipating a shock.
The current research examines the effect of CDP on the medial prefrontal firing rate in different situations. The rats are tested in both fear inducing and non fear inducing situations while on CDP. It has been established that CDP acts to reduce septal inhibition in anxiety provoking situations, so the current research examines whether this is the same in the medial prefrontal cortex. We suspect that CDP will reduce inhibition in a manner similar to the inhibition seen in the septum. We will be inserting eight recording electrodes into the medial prefrontal cortex of male rats and recording from single cells in the region. We will administer CDP to the animals, and then test their firing rates in an elevated plus maze, which has anxiety inducing open arms and more secure closed arms. We predict that CDP will cause a reduction in medial prefrontal area inhibition only when the rats are in the open arms; the anxiety provoking situation.