The Anxiogenic Effect of 5-HT on the Lateral Septum

Posted June 22nd, 2010 at 3:18 pm.

Abstract: Fatima Quadri and Jackline Barikdar
Mentor: Dr. Thomas
Previous research has shown that there is a reciprocal relationship between the amygdala and the Lateral Septum (LS), both located in the forebrain. Activation in the amygdala leads to increased levels of anxiety, which also promotes activation of the LS in a negative feedback response, thus reducing anxiety. The current research will focus on the serotonin (5-HT) 5HT1A autoreceptor, which inhibits the release of 5-HT in the forebrain. The forebrain receives its supply of 5-HT from the nucleus of Raphé, located in the brain stem. We hypothesize that increasing the levels of 5-HT to the LS will decrease its activity, and therefore increase activity of the amygdala, and leading to an anxiogenic, or anxiety increasing, response.

Anesthetized rats will be administered with 1-5 µg of an autoreceptor antagonist (WAY 100635) mixed with 0.5 µL of artificial cerebrospinal fluid through a cannula. The antagonist will bind to the 5HT1A autoreceptors and prevent them from inhibiting the release of 5-HT. This will increase the activity of the nucleus of Raphé as well as enhance 5-HT levels. The effects of the increased 5-HT levels to the LS will be measured using single cell recording. This type of recording measures the brain activity of specific neurons in the animal’s brain by inserting an electrode into the region of interest.

After the determination of how 5-HT levels affect LS activity, a conflict paradigm will be used with non-sedated rats. This kind of paradigm is a stress test for the animal: First, a thirsty animal is allowed to lick water freely for a certain amount of time. After the time limit, a tone will sound and indicate that the animal will be shocked after a certain number of licks. Typically licking behavior is reduced during this period in order to prolong or avoid the shock. The reduction of licking behavior is a result of increased activity in the amygdala, indicating anxiety or fear of the shock. However, the animal will lick more freely despite the shocks if amygdala activity is reduced. Decreased activity of the amygdala leads to a reduction of anxiety. The conflict paradigm will assess changes in licking behavior using a dose response curve for the antagonist. The interest of the study is to observe how increased activity in the nucleus of Raphé affects the reciprocal interaction of the amygdala and LS. The results can help analyze anxiety disorders in humans as well as aid in discovering potential treatments for them.

Filed under: 2010,Barikdar, Jackline,Quadri, Fatima,Thomas, Dr. Earl Tags: by Lisa Klinman

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