Effect of the 5-HT2C Receptor Agonist WAY-163909 on Serotonin and Dopamine Metabolism across the Rat Brain: A Quantitative and Qualitative Neurochemical Study
Abstract
:1. Introduction
2. Results
2.1. Quantitative Analysis of DA and 5-HT Metabolism after WAY-163909 Treatment
2.1.1. Pattern of Correlations of the 5-HIAA/5-HT Ratio across the Brain
2.1.2. Pattern of Correlations of the DOPAC/DA Ratio across the Brain
2.1.3. Pattern of Correlations between DOPAC/DA and 5-HIAA/5-HT Ratio across the Brain
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. Tissue Sampling and Conditioning
4.3. HPLC Analysis and Electrochemical Detection
4.4. Pharmacological Treatment and Experimental Design
4.5. Statistical Analysis of the Data
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
aCg | anterior cingulate cortex |
ains | anterior insular cortex |
BLA | basolateral nucleus of the amygdala |
CE | central nucleus of the amygdala |
CNS | central nervous system |
core | core of the nucleus accumbens |
DA | dopamine |
dHP | dorsal hippocampus |
DLO | dorsolateral orbitofrontal cortex |
DLS | dorsolateral striatum |
DMS | dorsomedial striatum |
DOPAC | 3,4-dihydroxyphenylacetic acid |
DR | dorsal raphe nucleus |
dHY | dorsal hypothalamus |
EPN | entodepuncular nucleus |
HPLC | high pressure liquid chromatography |
IL | infralimbic cortex |
LO | lateral orbitofrontal cortex |
M2 | motor cortex M2 |
MO | medial orbitofrontal cortex |
MR | median raphe nucleus |
pCg | posterior cingulate cortex |
pins | posterior insular cortex |
PL | prelimbic cortex |
5-HIAA | 5-hydroxyindole-3-acetic acid |
5-HT | 5-hydroxytryptamine; serotonin |
5-HT2C receptors | Serotonin 2C receptors |
shell | shell of the nucleus accumbens |
SN | substantia nigra |
STN | subthalamic nucleus |
vHP | ventral hippocampus |
vHY | ventral hypothalamus |
VCS | ventrocaudal striatum |
VLS | ventrolateral striatum |
VMS | ventromedial striatum |
VTA | ventral tegmental area |
WAY-163909 | (7bR,10aR)-1,2,3,4,8,9,10,10a-octahydro-7bH-cyclopenta-[b][1,4]diazepino[6,7, 1hi]indole] |
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Brain Regions | 5-HIAA | DOPAC | HVA | ||||||
---|---|---|---|---|---|---|---|---|---|
Saline | WAY 0.3 | WAY 3 | Saline | WAY 0.3 | WAY 3 | Saline | WAY 0.3 | WAY 3 | |
MO | 206 ± 30 | 224 ± 20 | 252 ± 19 | 122 ± 22 | 121 ± 15 | 180 ± 22 | 23.9 ± 3.12 | 91.4 ± 20 * | 103 ± 24 ** |
LO | 212 ± 34 | 188 ± 26 | 328 ± 54 | 35.8 ± 2.81 | 44.1 ± 15.3 | 66.1 ± 9.22 | nd | nd | nd |
DLO | 73.6 ± 11.9 | 37.1 ± 2.95 * | 59.1 ± 11.3 | 13.2 ± 2.88 | 12.6 ± 1.8 | 20.3 ± 3.92 | nd | nd | nd |
M2 | 92.2 ± 20.1 | 87.3 ± 12.6 | 104 ± 15.6 | 27.6 ± 3.09 | 20.9 ± 1.7 | 30.4 ± 5.76 | 1.82 ± 0.61 | 1.28 ± 0.34 | 1.99 ± 0.35 |
PL | 137 ± 10.9 | 149 ± 24.7 | 116 ± 13.9 | 9.12 ± 1.30 | 12.5 ± 3.43 | 9.71 ± 1.95 | 36.2 ± 11.7 | 103 ± 20.3 | 62.9 ± 19.7 |
IL | 147 ± 35.3 | 124 ± 19.1 | 121 ± 31.2 | 29.9 ± 5.16 | 19.4 ± 1.94 | 25.5 ± 6.39 | 18.5 ± 3.92 | 16.3 ± 3.21 | 24.6 ± 4.94 |
aCg | 336 ± 16.0 | 312 ± 72.6 | 228 ± 45.1 | 180 ± 14.1 | 118 ± 34.6 | 115 ± 27.5 | nd | nd | nd |
pCg | 386 ± 43.8 | 348 ± 34.5 | 308 ± 16.8 | 41.9 ± 3.28 | 38.0 ± 4.49 | 30.3 ± 1.46 | nd | nd | nd |
ains | 136 ± 18.9 | 113 ± 20 | 106 ± 11.8 | 24.5 ± 5.13 | 27.9 ± 4.72 | 21.2 ± 2.4 | 8.86 ± 2.75 | 6.67 ± 1.22 | 6.15 ± 0.71 |
pins | 99.6 ± 8.35 | 79 ± 11.7 | 102 ± 15.9 | 17.1 ± 4.1 | 15.2 ± 1.6 | 16.9 ± 3.63 | 3.98 ± 0.56 | 3.75 ± 0.76 | 4.22 ± 0.70 |
dHP | 81.8 ± 9.15 | 60.3 ± 8.36 | 81.8 ± 4.75 | 12.3 ± 0.34 | 14.24 ± 0.90 | 12.43 ± 0.67 | nd | nd | nd |
vHP | 159 ± 3.61 | 139 ± 17.6 | 132 ± 11.9 | 15.2 ± 2.2 | 15.5 ± 3.04 | 13.71 ± 4.2 | nd | nd | nd |
BLA | 151 ± 17.7 | 215 ± 25.9 | 229 ± 17.5 | 104 ± 53.9 | 116 ± 23.6 | 100 ± 32.7 | nd | nd | nd |
CE | 132 ± 18.6 | 199 ± 21.4 * | 108 ± 19.9 | 59.0 ± 10.0 | 131 ± 40.3 | 45.8 ± 13.9 | nd | nd | nd |
shell | 178 ± 17.5 | 123 ± 10.5 | 154 ± 16.1 | 728 ± 85.8 | 595 ± 73.0 | 726 ± 71.0 | 540 ± 83.6 | 449 ± 41.4 | 586 ± 52.8 |
core | 76.0 ± 6.36 | 63.8 ± 7.52 | 73.0 ± 11.1 | 847 ± 78 | 682 ± 106 | 825 ± 145 | 150 ± 9.02 | 124 ± 16.1 | 166 ± 23.5 |
VMS | 142 ± 23.8 | 137 ± 13.8 | 170 ± 23.5 | 480 ± 80.2 | 477 ± 72.6 | 569 ± 84.6 | 257 ± 56.7 | 272 ± 48.4 | 352 ± 107 |
VLS | 208 ± 12.3 | 244 ± 18.2 | 274 ± 28.2 | 876 ± 123 | 661 ± 49.6 | 799 ± 58.6 | 407 ± 62.8 | 363 ± 15.2 | 445 ± 36.6 |
DMS | 96.2 ± 15.9 | 85.6 ± 6.45 | 79.1 ± 7.23 | 709 ± 109 | 709 ± 98.6 | 720 ± 83.1 | 603 ± 95.8 | 667 ± 66.4 | 806 ± 59.0 |
DLS | 190 ± 66.9 | 110 ± 17.6 | 144 ± 20.3 | 797 ± 129 | 727 ± 92.5 | 838 ± 110 | 982 ± 93.3 | 827 ± 97.0 | 1113 ± 167 |
VCS | 172 ± 36.9 | 173 ± 38.4 | 250 ± 42.2 | 307 ± 65.4 | 272 ± 76.9 | 471 ± 82.6 | 359 ± 80.6 | 359 ± 96.8 | 521 ± 94.2 |
EPN | 147 ± 17.2 | 174 ± 25.8 | 111 ± 15.4 | 16.7 ± 2.92 | 18.6 ± 3.81 | 11.40 ± 2.11 | 1.76 ± 0.27 | 2.38 ± 0.65 | 1.79 ± 0.23 |
STN | 257 ± 43.4 | 260 ± 37.6 | 310 ± 34.9 | 132 ± 32.5 | 148 ± 22.6 | 181 ± 29.7 | 6.48 ± 2.15 | 7.57 ± 1.29 | 9.05 ± 1.40 |
vHY | 74.9 ± 8.82 | 54.3 ± 6.15 | 51.8 ± 8.67 | 28.2 ± 7.14 | 22.8 ± 4.02 | 25.0 ± 3.40 | nd | nd | nd |
dHY | 156 ± 23.6 | 101 ± 14.9 | 81 ± 21.6 | 3.16 ± 0.62 | 2.19 ± 0.52 | 2.41 ± 0.63 | 2.63 ± 0.77 | 1.86 ± 0.57 | 3.87 ± 1.29 |
SN | 738 ± 55.9 | 766 ± 47.9 | 754 ± 37.8 | 474 ± 82.4 | 436 ± 70.1 | 642 ± 61.7 | 194 ± 59.8 | 133 ± 34.5 | 176 ± 50.9 |
VTA | 428 ± 44.3 | 459 ± 41.4 | 385 ± 62.8 | 625 ± 64.3 | 650 ± 91.4 | 597 ± 67.6 | 83.0 ± 10.8 | 85.0 ± 8.17 | 75.4 ± 10.5 |
DR | 396 ± 32.6 | 373 ± 19.8 | 407 ± 33.1 | 23.2 ± 5.9 | 19.2 ± 3.9 | 31.9 ± 7.3 | nd | nd | nd |
MR | 318 ± 62 | 230 ± 35 | 265 ± 40.5 | 63.9 ± 18.8 | 107 ± 28.8 | 37.9 ± 19.2 | 15.4 ± 1.8 | 16.4 ± 2.9 | 9.13 ± 1.7 |
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Whitestone, S.; De Deurwaerdère, P.; Baassiri, L.; Manem, J.; Anouar, Y.; Di Giovanni, G.; Bharatiya, R.; Chagraoui, A. Effect of the 5-HT2C Receptor Agonist WAY-163909 on Serotonin and Dopamine Metabolism across the Rat Brain: A Quantitative and Qualitative Neurochemical Study. Int. J. Mol. Sci. 2019, 20, 2925. https://doi.org/10.3390/ijms20122925
Whitestone S, De Deurwaerdère P, Baassiri L, Manem J, Anouar Y, Di Giovanni G, Bharatiya R, Chagraoui A. Effect of the 5-HT2C Receptor Agonist WAY-163909 on Serotonin and Dopamine Metabolism across the Rat Brain: A Quantitative and Qualitative Neurochemical Study. International Journal of Molecular Sciences. 2019; 20(12):2925. https://doi.org/10.3390/ijms20122925
Chicago/Turabian StyleWhitestone, Sara, Philippe De Deurwaerdère, Lynn Baassiri, Julien Manem, Youssef Anouar, Giuseppe Di Giovanni, Rahul Bharatiya, and Abdeslam Chagraoui. 2019. "Effect of the 5-HT2C Receptor Agonist WAY-163909 on Serotonin and Dopamine Metabolism across the Rat Brain: A Quantitative and Qualitative Neurochemical Study" International Journal of Molecular Sciences 20, no. 12: 2925. https://doi.org/10.3390/ijms20122925