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The serotonergic system has been implicated in emotional and cognitive functions since early work. In particular, an important role has been attributed to the 5-HT2A receptor in schizophrenia, depression, eating disorders, and anxiety. The aim of the study was to evaluate the involvement of the brain 5-HT2A receptor in dogs with severe anxiety disorder, using 123 I-5I-R91150 and SPECT. Methods: SPECT was performed with the 5-HT2A receptor-specific radioligand 123 I-5I-R91150 to determine the 5-HT2A receptor binding index (BI) in the brains of dogs. Sixteen dogs with pathologic anxiety problems were compared with 22 normal-behaving reference dogs. Results: Lower 5-HT2A receptor BI was found in the left (P 5 0.001) and right (P 5 0.002) frontal cortices in the group of dogs with anxiety disorders than in the reference group. Right (P 5 0.022) and left (P 5 0.048) temporocortical BIs were also significantly lower in the dogs with anxiety disorders. Finally, the BI was significantly lower in the right occipital cortex (P 5 0.038) of dogs with anxiety disorders than in the reference dogs. After correction for multiple comparisons (P , 0.0056), only the bilateral frontocortical lower BI remained significant. Conclusion: The findings in this study indicate that the 5-HT2A receptor is involved in the pathophysiology of anxiety disorders in dogs. The affected brain regions are in concordance with the brain regions involved in human anxiety disorders. The acquired data confirm the potential of using the dog as a natural model for investigation of the different mechanisms of anxiety disorders. In this regard, the use of dogs may contribute to the development of novel treatment approaches and new drugs for veterinary and human use.

Alterations of regional brain activity in the prefrontal cortex and in limbic areas have been reported in humans with anxiety disorders. This animal study reports the results of brain perfusion imaging with single photon emission computed tomography (SPECT) in dogs with anxiety disorders. Based on the human literature, we hypothesized altered prefrontal and higher temporal brain perfusion. SPECT acquisitions were performed using the 99m Tc-labelled tracer ethyl cysteinate dimer (ECD). Eighteen dogs with pathological anxiety were compared with 18 normally behaving reference dogs. We found, in the group of dogs with anxiety disorders, lower perfusion in the left frontal cortex (p=0.003), in the subcortical region (p= 0.007) and increased perfusion in the right (p=0.05) temporal cortex. Taken together, our rCBF findings are suggestive for a dysfunction of the prefrontal cortex and the limbic system in canine anxiety disorders.

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