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Prevention of depressive behaviour in the YAC128 mouse model of Huntington disease by mutation at residue 586 of huntingtin

Pouladi M, Graham RK, Karasinska JM, Xie Y, Dar Santos R, Petersén Å, and Hayden MR

1 Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, V6T 1Z3 Canada 2 Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Vancouver, British Columbia, V5Z 4H4 Canada 3 Translational Neuroendocrine Research Unit, Department of Experimental Medical Science, Lund University, 221 84 Sweden

Brain 132 (4): 919-932 (2009)


The neurobiological bases of mood disorders remain elusive but both monoamines and neuropeptides may play important roles. The neuropeptide cocaine and amphetamine regulated transcript (CART) was shown to induce anxiety-like behavior in rodents, and mutations in the human CART gene are associated with depression and anxiety. We measured CART-like immunoreactivity (-LI) in genetic rat models of depression and anxiety, i.e. the Flinders Sensitive Line (FSL) and rats selected for High Anxiety-related Behavior (HAB) using a radioimmunoassay. CART-LI was significantly increased in the periaqueductal grey in FSL rats, whereas in the HAB strain it was increased in the hypothalamus, both compared with their respective controls. No line-dependent changes were found in the hippocampus, striatum or frontal cortex. Our results confirm human genetic studies indicating CART as a neurobiological correlate of depression and anxiety, and suggest that its differential regulation in specific brain regions may play a role for the behavioral phenotypes.