ANXIOGENIC AND DEPRESSIVE-LIKE BEHAVIOR IN CB1+/- AND CB1-/- MICE

SORIANO, DELIA; CALTANA LAURA; BRUSCO ALICIA

Madrid

Congreso; 19 Reunión Anual de la Sociedad Española de Investigacion sobre Cannabinoides; 2018

Sociedad Española de Investigación sobre Cannabinoides

The neuromodulatory role of the endocannabinoid system contributes on maintaining the homeostasis of physiological states including mood and emotion. Changes in the expression of the CB1 receptor (CB1R) gene have been related to mood disorders and depression. Mice lacking CB1R (CB1-/-) exhibited a behavioral state analogous to depression. Previous studies of our group, showed that CB1-/- mice presents alterations in neuronal cytoskeleton, dendritic structure and synaptic morphology in the hippocampus and these changes could be related with alterations in neuronal plasticity.Heterozygous CB1 receptor knockout mice (CB1+/-) exhibited approximately 50% lower expression levels of CB1R in brain areas such as the cerebellum, hippocampus, striatum and cingulate cortex. Similar changes were found in human brains of chronic users of cannabis and in animal models of cannabinoid agonists chronic exposure. The aim of the study is to evaluate the effects of deficiency of CB1R in behavioral paradigms of anxiety and depression in CB1 receptor wild-type mice (CB1+/+), CB1+/- and CB1-/-.Mice were tested in a large behavioral test battery: open field (OF), light-dark box (LDB), novelty-suppressed feeding (NSF), sucrose splash and finally forced swimming test (FST). Mice spent a day of resting time between consecutive tests. In OF, time spent in periphery was increased in CB1-/- meanwhile number of entries and time spent in central zone decreased in CB1-/- and CB1+/-. In LDB, time spent in the dark chamber increased only in CB1-/-. In OF and LDB, motor activity decreased in CB1-/-. In the case of NSF test no observed differences in CB1-/- and CB1+/-. In sucrose splash test, latency to the first groom was higher in CB1+/-. In FST, time of immobilization showed a tendency to increase in CB1-/- meanwhile number of episodes of immobilization decreased in CB1-/-.Then, complete and partial deficiency in CB1 receptor expression could explain the behavioral phenotype observed in mice and, could be correlate with anxious and depressive behavior reported in chronic cannabis smokers.