Endocannabinoids render exploratory behaviour largely independent of the test aversiveness: role of glutamatergic transmission.

To investigate the impact of averseness, controllability and familiarity of a test situation on the involvement of the endocannabinoid system in the regulation of exploratory behaviour, we tested conventional and conditional cannabinoid receptor type 1 (CB1)-deficient mice in behavioural paradigms with different emotional load, which depended on the strength of illumination and the ability of the animals to avoid the light stimulus. Complete CB1 null-mutant mice (Total-CB1-KO) showed an anxiogenic-like phenotype under circumstances where they were able to avoid the bright light such as the elevated plus-maze and the light/dark avoidance task. Conditional mutant mice lacking CB1 expression specifically in cortical glutamatergic neurons (Glu-CB1-KO), in contrast, failed to show a similar phenotype under the same experimental conditions. However, both mutant lines showed increased avoidance of open arm exploration during a second exposure to the elevated plus-maze. If tested in situations where the fear eliciting light could not be avoided, Total-CB1-KO mice showed increased thigmotaxis in an open field, decreased social investigation and decreased novel object exploration under aversive light conditions, but not under non-aversive low light. This time, Glu-CB1-KO also showed decreased exploratory behaviour towards objects and conspecific juveniles and increased thigmotaxis in the open field. Taking into consideration that the behavioural performance of wild-type mice was only marginally affected by changes in light intensities, these data indicate that the endocannabinoid system renders exploratory behaviour largely independent of the test averseness. This process differentially involves endocannabinoid-controlled glutamatergic transmission, depending on the controllability of the test situation.