| Abstract No.: | B-C2077 |
| Country: | Canada |
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| Title: | NEUROPEPTIDE Y Y1 AND Y2 RECEPTORS MEDIATE ANXIOLYTIC- AND ANTIDEPRESSANT-LIKE BEHAVIORS IN THE OLFACTORY BULBECTOMIZED RAT MODEL OF DEPRESSION |
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| Authors/Affiliations: | 1 Julio César Morales-Medina*; 4 Yvan Dumont; 4 Stéphane Bastianetto; 2 Charles Etienne Benoit; 2 Philippe Sarret; 3 Rémi Quirion;
1 Department of Neurology & Neurosurgery, McGill University, Douglas Mental Health University Institute, Montreal, QC, Canada; 2 Department of Physiology and Biophysics, Faculty of Medicine and Health Sciences, University of Sherbrooke, QC, Canada; 3 Douglas Mental Health University Institute, Department of Psychiatry, McGill University, QC, Canada ; 4 Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada
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| Content: | Depression is an heterogeneous debilitating disorder that will become the world's second leading cause of disabilities by 2020. In addition, eight percent of Canadian population experiences a major depression in their lifetime (Quick Facts: Mental Illness and Addiction in Canada, Mood Disorders Society of Canada, 2006). Neuropeptide Y (NPY) is broadly distributed in the CNS (Kask et al., Neurosci Biobehav Rev, 26, 2002). Animal and pre-clinical studies suggested that NPY and its receptors may be involved in mood-related disorders (Heilig M, Neuropeptides, 38, 2004; Redrobe et al., Neuropsychopharm, 26, 2002). The olfactory bulbectomy (OBX) rat model produces behavioral, immunological and neurochemical alterations similar to those observed in the human condition (Kelly JP et al., Pharmacol & Ther, 74, 1997). Objectives: Using the OBX rat model, we studied the in vivo effects of the Y1-like receptor agonist, [Leu31,Pro34] PYY and the Y2 receptor antagonist, BIIE0246, in emotion-like behavioral tests. Materials and Methods: Sprague-Dawley male rats (150-165g) were used for OBX or sham operations as previously described (Hasegawa et al., Psychopharmacology, 179, 2005). OBX rats received intracerebroventricular (ICV) administration of either [Leu31,Pro34] PYY, (0.1, 0.3, 1.0, and 3.0 nmol/day), BIIE0246, (1, 3, 10 nmol/day) or vehicle for 14 days prior to behavioral testing. Sham animals received ICV administration of either saline or DMSO/saline. We used well-established tests for assessing anxiety-like (open field, OF; and social interaction, SI) and depression-like (forced swim test, FST) behaviors. Results: OBX rats treated with [Leu31,Pro34] PYY showed improved of behavioral deficits in the FST and SI paradigms. [Leu31,Pro34] PYY also reduced both hyperlocomotion and anxiety-coping behaviors in the OF. The Y2 antagonist BIIE0246 improved depression-like behaviors in the FST while had little impact on anxiety-like paradigms in OBX animals. Conclusion: These results provide further evidence that NPY Y1 and Y2 receptors play a significant role in emotion-related behaviors and suggest that these receptors may represent promising targets as novel anxiolytic and antidepressant treatments.
Supported by: Canadian Institutes of Health Research to RQ and CONACyT-Mexico JCMM.
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