Communication and social interaction in the cannabinoid‐type 1 receptor null mouse: Implications for autism spectrum disorder

William Fyke, Marika Premoli, Victor Echeverry Alzate, José A. López‐Moreno, Valerie Lemaire‐Mayo, Wim E. Crusio, Giovanni Marsicano, Markus Wöhr, Susanna Pietropaolo
Autism Research. 2021-06-26; 14(9): 1854-1872
DOI: 10.1002/aur.2562

Read on PubMed

Fyke W(1)(2), Premoli M(3), Echeverry Alzate V(4)(5), López-Moreno JA(4), Lemaire-Mayo V(1), Crusio WE(1), Marsicano G(6), Wöhr M(7)(8)(9)(10), Pietropaolo S(1).

Author information:
(1)University of Bordeaux, CNRS, EPHE, INCIA, UMR 5287, Bordeaux, France.
(2)Graduate Program in Neural and Behavioral Science, SUNY Downstate Medical
Center, Brooklyn, New York, USA.
(3)Department of Molecular and Translational Medicine, University of Brescia,
Brescia, Italy.
(4)Department of Psychobiology and Methodology on Behavioral Sciences, Faculty
of Psychology, Madrid Complutense University, Spain.
(5)Unidad Gestión Clínica de Salud Mental, Instituto de Investigación Biomédica
de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Malaga University,
(6)University of Bordeaux, INSERM, U862 NeuroCentre Magendie, Group
Endocannabinoids and Neuroadaptation, Bordeaux, France.
(7)KU Leuven, Faculty of Psychology and Educational Sciences, Research Unit
Brain and Cognition, Laboratory of Biological Psychology, Social and Affective
Neuroscience Research Group, Leuven, Belgium.
(8)KU Leuven, Leuven Brain Institute, Leuven, Belgium.
(9)Faculty of Psychology, Experimental and Biological Psychology, Behavioral
Neuroscience, Philipps-University of Marburg, Marburg, Germany.
(10)Center for Mind, Brain and Behavior, Philipps-University of Marburg,
Marburg, Germany.

Clinical and preclinical findings have suggested a role of the endocannabinoid
system (ECS) in the etiopathology of autism spectrum disorder (ASD). Previous
mouse studies have investigated the role of ECS in several behavioral domains;
however, none of them has performed an extensive assessment of social and
communication behaviors, that is, the main core features of ASD. This study
employed a mouse line lacking the primary endocannabinoid receptor (CB1r) and
characterized ultrasonic communication and social interaction in CB1-/- , CB1+/-
, and CB1+/+ males and females. Quantitative and qualitative alterations in
ultrasonic vocalizations (USVs) were observed in CB1 null mice both during early
development (i.e., between postnatal days 4 and 10), and at adulthood (i.e., at
3 months of age). Adult mutants also showed marked deficits in social interest
in the three-chamber test and social investigation in the direct social
interaction test. These behavioral alterations were mostly observed in both
sexes and appeared more marked in CB1-/- than CB1+/- mutant mice. Importantly,
the adult USV alterations could not be attributed to differences in anxiety or
sensorimotor abilities, as assessed by the elevated plus maze and auditory
startle tests. Our findings demonstrate the role of CB1r in social communication
and behavior, supporting the use of the CB1 full knockout mouse in preclinical
research on these ASD-relevant core domains. LAY SUMMARY: The endocannabinoid
system (ECS) is important for brain development and neural function and is
therefore likely to be involved in neurodevelopmental disorders such as Autism
Spectrum Disorder (ASD). Here we investigated changes in social behavior and
communication, which are core features of ASD, in male and female mice lacking
the chief receptor of this system. Our results show that loss of this receptor
results in several changes in social behavior and communication both during
early development and in adulthood, thus supporting the role of the ECS in these
ASD-core behavioral domains.

© 2021 International Society for Autism Research and Wiley Periodicals LLC.


Know more about