Low Basal CB2R in Dopamine Neurons and Microglia Influences Cannabinoid Tetrad Effects
Abstract
:1. Introduction
2. Results
2.1. CB1R and CB2R Expression in Liver, Cortex, and Spleen
2.2. CB1R and CB2R Expression in Hepatocytes, Neurons, and Microglia
2.3. CB1R and CB2R Cannabinoidergic Neurons
2.4. Generation of Cnr1f/f, Cnr2f/f, Abl-Cnr1Δ, and Dat-Cnr2Δ Mouse Strains
2.5. Tetrad and Alcohol Effects Following Deletion of CB2Rs in Dopamine Neurons and Microglia
3. Discussion
4. Materials and Methods
4.1. Animals and Isolation of Hepatocytes, Neurons, and Microglia
4.2. RNA Isolation and TaqMan RT-qPCR, RT-preAmp-qPCR Assays
4.3. RNAscope In Situ Hybridization (ISH)
4.4. Generation Cnr1f/f and Cnr2f/f Mouse Strains
4.5. Generation of Abl-Cnr1Δ, Dat-Cnr2Δ, and Cx3cr1-Cnr2Δ Recombinant Strains
4.6. Behavioral Assays
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ACEA | Aarachidonyl 2′ chloroethylamide |
ANOVA | Analysis of variance |
CB1R | Cannabinoid type 1 receptor |
CB2R | Cannabinoid type 2 receptor |
Cnr1 | Mouse cannabinoid receptor 1 gene symbol |
Cnr2 | Mouse cannabinoid receptor 2 gene symbol |
cKO | Conditional knockout |
Cnr1ff | Cannabinoid receptor 1 floxed |
Cnr2ff | Cannabinoid receptor 2z floxed |
CPP | Conditioned place preference |
Ct | Cycle threshold |
Cx3cr1 | Chemokine receptor1 |
DAT | Dopamine transporter |
DSI | Depolarization-induced suppression of inhibition |
DSE | Depolarization-induced suppression of excitation |
DMSO | Dimethyl sulfoxide |
ECS | Endocannabinoid system |
eGFP | Enhanced green fluorescence protein |
ESCs | Embryonic stem cells |
FACS | Fluorescence-activated cell sorting |
FITC | Fluorescein isothiocyanate |
gKO | Germline knockout |
GFP | Green fluorescence protein |
GPCR | G-protein coupled receptor |
Hep-cKO | Hepatocyte conditional knockout |
HFHS | High-fat high sugar |
ISH | In situ hybridization |
NIS | Sodium iodide transporter |
ORF | Open reading frame |
PE | Phycoerythrin |
RT–PCR | Real-time polymerase chain reaction |
SYN-Cnr2 | CB2R deletion from synapse |
Δ9-THC | Delta-9-tetrahydrocannabinol |
TH | Tyrosine hydroxylase |
UTR | Untranslated region |
VGLUT2 | Vesicular glutamate transporter |
VTA | Ventral tegmental area |
WT | Wild type |
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Dat-Cnr2Δ | Main Effect of Drugs | Main Effect of Genotypes | Interaction |
---|---|---|---|
a Locomotion | F (1, 14) = 2.583 p = 0.1303 | F (2.217, 31.04) = 39.01 p < 0.0001 | F (3, 42) = 4.017 p = 0.0134 |
a Temperature | F (1, 14) = 0.2189 p = 0.6471 | F (2.481, 34.73) = 435.1 p < 0.0001 | F (3, 42) = 4.240 p = 0.0105 |
a Nociception | F (1, 14) = 62.10 p < 0.0001 | F (1.820, 25.48) = 34.80 p < 0.0001 | F (3, 42) = 12.34 p < 0.0001 |
a Catalepsy | F (1, 14) = 31.49 p < 0.0001 | F (2.151, 30.12) = 181.8 p < 0.0001 | F (3, 42) = 2.382 p = 0.0830 |
a Ethanol 8% | F (1, 18) = 27.88 p < 0.0001 | F (1, 18) = 143.7 p < 0.0001 | F (1, 18) = 114.7 p < 0.0001 |
Cx3cr1-Cnr2Δ | |||
a Locomotion | F (1, 14) = 0.09896 p = 0.7577 | F (2.058, 28.81) = 191.3 p < 0.0001 | F (4, 56) = 7.032 p = 0.0001 |
a Temperature | F (1, 14) = 2.516 p = 0.1350 | F (2.567, 35.94) = 33.74 p < 0.0001 | F (4, 56) = 3.120 p = 0.0218 |
b Nociception | F (1, 69) = 1.196 p > 0.05 | F (2.221, 38.31) = 380.4 p < 0.0001 | F (4, 69) = 2.999 p < 0.05 |
b Catalepsy | F (1, 14) = 0.6054 p > 0.05 | F (2.387, 32.22) = 1.676 p > 0.05 | F (4, 54) = 6.708 p < 0.05 |
a Ethanol 8% | F (1, 18) = 3.369 p = 0.0830 | F (1, 18) = 317.4 p < 0.0001 | F (1, 18) = 11.35 p = 0.0034 |
Alleles | TaqMan Probe or PCR Fragment | Forward Primer | Reverse Primer |
---|---|---|---|
Cnr1-wt | CATCTGTTGGTGATTTCT(FAM) | CCTAAGAACTGCATGGCATGAAG | GCTGGGAACCCCAAATGGT |
Cnr1-flox | CTAGCATCTGTTGGAGTGTAC(VIC) | CCTAAGAACTGCATGGCATGAAG | GGAACTTCGCTAGACTAGTACGC |
Cnr2-wt | AGTCTTCAGAGAACTCT(FAM) | GCTGGGTTCACTGGAGGTACA | ACACAGCAAAATGTCACAAGGAA |
Cnr2-flox | AGTCTTCAATTGCGTACGTT(VIC) | GCTGGGTTCACTGGAGGTACA | CGCGACACGGACACAATC |
Cnr2-wt | 386 bp PCR FRAGMENT | GGTCAAGAATTATGATGCCCTAAGGACC | CCCAACTCCTTCTGCTTATCCTTCAGG |
Cnr2-flox | 545 bp PCR FRAGMENT | GGTCAAGAATTATGATGCCCTAAGGACC | CCCAACTCCTTCTGCTTATCCTTCAGG |
Abl-wt | CCTGTCATGCCCACACAAATCTCTCC(FAM) | GCTGTCATCTCTTGTGGGCTGT | ACTCATGGGAGCTGCTGGTTC |
Abl-Cre | CTATCAACCCCGGGATCC(VIC) | AGCGAGTCTTTCTGCACACA | GCTGCAGGTCGACTCTAGATC |
Dat-wt | AGATCACAAAGGAAACC(FAM) | GCCAGCTGGGCCATCTC | AAGTGGCCCTCCTTTCTTGAC |
Dat-Cre | CCCCCCTAACGTTACT(VIC) | GTTGGTGTAAAGTGGAAGGAGACA | CGCACACCGGCCTTATTC |
Cx3cr1-wt | 380 bp PCR FRAGMENT | AGCTCACGACTGCCTTCTTC | GCAGGGAAATCTGATGCAAG |
Cx3cr1-Cre | 816 bp PCR FRAGMENT | GACATTTGCCTTGCTGGAC | GCAGGGAAATCTGATGCAAG |
Cre | GGTTAGCACCGCAGG(VIC) | TTAATCCATATTGGCAGAACGAAAACG | CAGGCTAAGTGCCTTCTCTACA |
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Liu, Q.-R.; Canseco-Alba, A.; Liang, Y.; Ishiguro, H.; Onaivi, E.S. Low Basal CB2R in Dopamine Neurons and Microglia Influences Cannabinoid Tetrad Effects. Int. J. Mol. Sci. 2020, 21, 9763. https://doi.org/10.3390/ijms21249763
Liu Q-R, Canseco-Alba A, Liang Y, Ishiguro H, Onaivi ES. Low Basal CB2R in Dopamine Neurons and Microglia Influences Cannabinoid Tetrad Effects. International Journal of Molecular Sciences. 2020; 21(24):9763. https://doi.org/10.3390/ijms21249763
Chicago/Turabian StyleLiu, Qing-Rong, Ana Canseco-Alba, Ying Liang, Hiroki Ishiguro, and Emmanuel S. Onaivi. 2020. "Low Basal CB2R in Dopamine Neurons and Microglia Influences Cannabinoid Tetrad Effects" International Journal of Molecular Sciences 21, no. 24: 9763. https://doi.org/10.3390/ijms21249763
APA StyleLiu, Q. -R., Canseco-Alba, A., Liang, Y., Ishiguro, H., & Onaivi, E. S. (2020). Low Basal CB2R in Dopamine Neurons and Microglia Influences Cannabinoid Tetrad Effects. International Journal of Molecular Sciences, 21(24), 9763. https://doi.org/10.3390/ijms21249763