Control of exploration, motor coordination and amphetamine sensitization by cannabinoid CB1 receptors expressed in medium spiny neurons. (13th July 2021)

• Record Type: Journal Article
• Authors: Bonm, Alipi V.; Elezgarai, Izaskun; Gremel, Christina M.; Viray, Katie; Bamford, Nigel S.; Palmiter, Richard D.; Grandes, Pedro; Lovinger, David M.; Stella, Nephi
• Is Part Of: European journal of neuroscience. Volume 54:Number 3(2021)
• Page Start: 4934
• Page End: 4952
• Publication Date: 2021-07-13
• Subjects: endocannabinoid -- genetically modified -- globus pallidus -- mouse line -- substantia nigra; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.15381
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: Activation of cannabinoid 1 receptors (CB1 R) modulates multiple behaviours, including exploration, motor coordination and response to psychostimulants. It is known that CB1 R expressed by either excitatory or inhibitory neurons mediates different behavioural responses to CB1 R activation, yet the involvement of CB1 R expressed by medium spiny neurons (MSNs), the neuronal subpopulation that expresses the highest level of CB1 R in the CNS, remains unknown. We report a new genetically modified mouse line that expresses functional CB1 R in MSN on a CB1 R knockout (KO) background (CB1 R(MSN) mice). The absence of cannabimimetic responses measured in CB1 R KO mice was not rescued in CB1 R(MSN) mice, nor was decreased spontaneous locomotion, impaired instrumental behaviour or reduced amphetamine‐triggered hyperlocomotion measured in CB1 R KO mice. Significantly, reduced novel environment exploration of an open field and absence of amphetamine sensitization (AS) measured in CB1 R KO mice were fully rescued in CB1 R(MSN) mice. Impaired motor coordination in CB1 R KO mice measured on the Rotarod was partially rescued in CB1 R(MSN) mice. Thus, CB1 R expressed by MSN control exploration, motor coordination, and AS. Our study demonstrates a new functional roles for cell specific CB1 R expression and their causal link in the control of specific behaviors. Abstract : We developed and validated a new genetically modified mouse line that expresses functional cannabinoid receptors 1 (CB1 R) in medium spiny neurons (MSNs, brain areas and projecting arrows are highlighted in blue) on a CB1 R knockout (KO) background (black brain areas and mouse), here referred to as CB1 R(MSN) mice. We studied mouse behaviors known to require functional CB1 R as determined by previous CB1 R knockout studies, and found that CB1 R expressed by MSN control exploration, motor coordination, and amphetamine sensitization. Our study demonstrates a new functional roles for CB1 R expressed by MSNs, the neuronal subpopulation that expresses the highest level of CB1 R in the CNS.