Veterinary/zoology session

Previous studies showed that the endocannabinoid system affects the development of anxious states. However the results are contradictory and it seems that the effect of pharmacological agents acting through the endocannabinoid system depends on the experimental context and the animal model used in the experiment. We hypothesize that the endocannabinoid activity principally affects the behavoiural reactivity, i.e. the changing of the environmental context can alter the behavioural effects of cannabinoids. We studied this hypothesis in two approaches. First we investigated the effects of pharmacologically increased endocannabinoid activity and then the decreased endocannabinoid activity by disrupting the CB1 cannabinoid receptor gene. We studied the effect of increased endocannabinoid activity in Sprague-Dawley rats. Animals were treated with URB597 a compound inhibiting the metabolism of the endocannabinoid anandamide, then anxiety and locomotion were measured in the elevated plus-maze test. To consider the environmental context animals underwent test in dark or in a more stressful light illumination and we investigated the effect of habituation of the animals for test conditions previous to the test. Results showed that if animals were habituated, anxiety did not change after URB597 treatment in light, but it increased in dark. However if there was no habituation URB597 had no effect in dark but it decreased anxiety in light illumination. A metaanalysis of all the data showed that animals receiving vehicle treatment reacted intensely for the experimental context, but increasing of the endocannabinoid activity cleared these reactions, i.e. anxiety of animals treated with URB597 changed more mildly with environmental conditions. We studied the effects of decreased endocannabinoid activity on behavioural reactivity with CB1 cannabinoid receptor knock-out (CB1 KO) and wild type mice. In a habituation test we investigated the changes in anxiety in the open-field test carried out in the same box during a three day period. We considered the experimental contexts, animals underwent test in dark or in light illumination. Results showed that lacking in CB1 receptor had no effects on anxiety and locomotion itself but CB1 KO animals reacted more intensely to environmental conditions (illumination) and show higher behavioural changes during the days than wild type mice. These data suggest that increase or decrease in endocannabinoid activity does not alter the anxiety in general but it alters the behavioural reactivity of stress. These findings could contribute to the understanding of the behavioural effects of the endocannabinoid system and the rethink of the contradictions in the literature.