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Autoradiographic study of the functionality of brain cannabinoid CB1- receptors in the olfactory bulbectomized rat and the modulation by chronic fluoxetine

AutorDíaz, Álvaro ; Rodríguez-Gaztelumendi, A. ; Rojo, María Luisa ; Pazos, Ángel
Fecha de publicación2009
EditorSociety for Neuroscience
CitaciónNeuroscience 2009
ResumenPreclinical and clinical evidences demonstrate an interaction between 5-HT neurotransmission and endocannabinoid signalling that might be relevant to understand the neurobiology and treatment of human depression. Animal models replicating the pathophysiological changes present in depressed patients may help to unravel adaptive changes underlying chronic antidepressant-induced responses. The aim of this work was to study the functionality of cannabioid CB1 brain receptors and its modulation after chronic fluoxetine treatment (10 mg/kg/day, s.c. 14 days) in the olfactory bulbectomized rat (OB), an animal model of chronic depression/anxiety. OB-induced hyperactivity in the open field was attenuated by chronic fluoxetine whereas no behavioural effects of the antidepressant were observed in control animals. CB1- receptor functionality in rat brain sections was assessed measuring the stimulation of [35S]GTPγS binding induced by the cannabinoid agonist WIN55212,2 (10 μM). In OB rats, CB1 receptor-mediated stimulation of [35S]GTPγS binding was increased in comparison with control animals in several brain areas: prefrontal cortex (% over basal binding = 225.3±29.4 vs 84.5±18.8; p<0.001), cingulate cortex (165.9±25.8 vs 44.7±9.8; p<0.01), CA1-field of hippocampus (164.5±19.6 vs 9.0±8.1; p<0.001), dentate gyrus (165.6±24.1 vs 29.5±6.4; p<0.001), amygdala (163.1±41.7 vs 49.1±20.4; p<0.01), substantia nigra (351.9±24.8 vs 151.9±22.9; p<0.01) and enthorrinal cortex (202.5±40.1 vs 65.2.5±24.2; p<0.01). Interestingly, chronic fluoxetine modulated CB1 receptors functionality in OB rats since a significant desensitization of WIN55212,2-induced G-protein activation was observed in fluoxetinetreated OB rats in prefrontal (155.1±8.5; p<0.5 vs non-treated OB-rats) and enthorrinal cortices (94.5±18.2; p<0.5 vs non-treated OB-rats) whereas it did not produce any change in control animals. Thus, olfactory bulbectomy induces a regional-selective up-regulation upon CB1 receptors functionality, particularly in depression-related brain areas. Moreover, the behavioural antidepressant-like effect of chronic fluoxetine in the >open field> test is associated with a reversal of those OB-induced adaptive changes upon CB1 receptors functionality in areas such as prefrontal and enthorrinal cortices. Our findings reinforce the utility of this animal model to further investigating the implication of the endocannabinoid system in the modulation of emotional processes and its potential role in the adaptive responses to chronic antidepressants.
DescripciónTrabajo presentado al 39th annual meeting Neuroscience celebrado en Chicago del 17 al 21 de octubre de 2009.
URIhttp://hdl.handle.net/10261/78871
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