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Evaluation of the Brain 5-HT2A Receptor Binding Index in Dogs with Anxiety Disorders, Measured with ¹²³I-5I-R91150 and SPECT

¹ Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium; ² Department of Psychiatry and Medical Psychology, Faculty of Medical and Health Sciences, Ghent University, Ghent, Belgium; and ³ Laboratory of Radiopharmacy, Pharmaceutical Sciences, Ghent University, Ghent, Belgium

Correspondence: For correspondence or reprints contact: Simon Vermeire, Department of Veterinary Medical Imaging and Small Animal Orthopaedics, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133 9820, Merelbeke, Belgium. E-mail: simon.vermeire{at}ugent.be

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 ¹²³I-5I-R91150 and SPECT. Methods: SPECT was performed with the 5-HT2A receptor-specific radioligand ¹²³I-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 = 0.001) and right (P = 0.002) frontal cortices in the group of dogs with anxiety disorders than in the reference group. Right (P = 0.022) and left (P = 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 = 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.

Key Words: anxiety disorders • SPECT • serotonin (5-HT) • 5-HT2A receptor • dog

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