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Control of exploration, motor coordination and amphetamine sensitization by cannabinoid CB 1 receptors expressed in medium spiny neurons
Author(s) -
Bonm Alipi V.,
Elezgarai Izaskun,
Gremel Christina M.,
Viray Katie,
Bamford Nigel S.,
Palmiter Richard D.,
Grandes Pedro,
Lovinger David M.,
Stella Nephi
Publication year - 2021
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.15381
Subject(s) - medium spiny neuron , amphetamine , cannabinoid , motor coordination , chemistry , sensitization , cannabinoid receptor , excitatory postsynaptic potential , receptor , knockout mouse , neuroscience , pharmacology , biology , agonist , biochemistry , basal ganglia , central nervous system , dopamine
Activation of cannabinoid 1 receptors (CB 1 R) modulates multiple behaviours, including exploration, motor coordination and response to psychostimulants. It is known that CB 1 R expressed by either excitatory or inhibitory neurons mediates different behavioural responses to CB 1 R activation, yet the involvement of CB 1 R expressed by medium spiny neurons (MSNs), the neuronal subpopulation that expresses the highest level of CB 1 R in the CNS, remains unknown. We report a new genetically modified mouse line that expresses functional CB 1 R in MSN on a CB 1 R knockout (KO) background (CB 1 R (MSN) mice). The absence of cannabimimetic responses measured in CB 1 R KO mice was not rescued in CB 1 R (MSN) mice, nor was decreased spontaneous locomotion, impaired instrumental behaviour or reduced amphetamine‐triggered hyperlocomotion measured in CB 1 R KO mice. Significantly, reduced novel environment exploration of an open field and absence of amphetamine sensitization (AS) measured in CB 1 R KO mice were fully rescued in CB 1 R (MSN) mice. Impaired motor coordination in CB 1 R KO mice measured on the Rotarod was partially rescued in CB 1 R (MSN) mice. Thus, CB 1 R expressed by MSN control exploration, motor coordination, and AS. Our study demonstrates a new functional roles for cell specific CB 1 R expression and their causal link in the control of specific behaviors.