Keywords: Corticotrophin Releasing Factor, Fear, Stress, GABA, Anxiety, Sex Differences, HPA Axis

Corticotrophin releasing factor (CRF), a peptide secreted by the paraventricular nucleus (PVN) of the hypothalamus, modulates the endocrine, autonomic, and behavioral responses to stress. The CRF receptor is expressed in a heterogeneous array of cell types, impeding advancement towards determining the mechanisms of fear and anxiety. As a way to explore the different components of the CRF system, we utilized a floxed GABA_b transgenic mouse crossed with a CRF-Cre driven mouse. This crossing allowed us to knockout GABA_B receptors in CRF-expressing neurons. CRF GABA_b Knockout mice were trained in context fear conditioning, cued fear conditioning, and assessed in anxiety measures including the open field and elevated plus maze. We expected the lack of GABA_B receptors would result in increased fear and anxiety as GABA is the main inhibitory neurotransmitter in the brain. CRF GABA_b Knockout males, but not females, display less context and cued fear as measured by freezing levels than wildtype littermates. Additionally, female knockout mice, but not males, displayed significantly less anxiety in the elevated plus maze. These data indicate that lacking CRF-containing GABA_b neurons disrupts anxiety-induced and fear behavior in the opposite direction of our prediction. Further research into the acquisition, consolidation, and extinction of condition fear can help to explain the mechanisms for pathological conditions and further treatment methodology.