Changements dans le circuit de la récompense suite à la bulbectomie olfactive : une nouvelle approche pour étudier des antidépresseurs
Depression is a chronic, recurrent and potentially deadly disorder that affects over 20 % of the population worldwide. The mechanisms underlying depression are still not understood and current pharmacotherapy, based largely on monoaminergic hypotheses, is plagued by suboptimal efficacy and delayed therapeutic latency.  This has lead to a search for novel pharmacological treatments. To achieve this, it is first necessary to develop adequate experimental tools.  With this in mind, we aimed to measure anhedonia, a cardinal symptom of depression, in laboratory rats.  We defined anhedonia as a reduction in reward, and measured it with the sucrose intake test and in the intracranial self-stimulation paradigm. In order to induce anhedonia, we surgically removed the olfactory bulbs, a procedure that results in a host of behavioral, cellular and biochemical changes that are qualitatively similar to those observed in clinical depression.  These changes are long-lasting and reversed by chronic antidepressant treatment, validating olfactory bulbectomy as an animal model of depression. Our results show that olfactory bulbectomy also produces anhedonia, reflected by a stable and long-lasting reduction in sucrose intake as well as a reduction in the rewarding effectiveness of amphetamine in the self-stimulation paradigm.  These effects were present even after three to four weeks post-surgery. Olfactory bulbectomy was also associated with increased striatal cAMP response element binding, a molecular index associated with depressive-like behaviour.  These findings suggest that anhedonia can be reliably produced and studied within the olfactory bulbectomy model and that reward circuitry may comprise a logical target for novel drugs to treat depression.
depression anhedonia olfactory bulbectomy antidepressants reward animal model