Acute and Chronic Nicotine Exposures Differentially Affect Central Serotonin 2A Receptor Function: Focus on the Lateral Habenula
Abstract
:1. Introduction
2. Results
2.1. Effect of Systemic Administration of Acute and Chronic Nicotine on 5-HT2AR Immunohistochemistry Expression in the LHb
2.2. 5-HT2AR Electrophysiology Experiments
2.2.1. Electrophysiological Characteristics of Spontaneously Active the LHb Neurons
2.2.2. Effect of Systemic Administration of 5-HT2AR Agonist TCB-2 on the Firing Rate and Pattern of LHb Neurons of Acute and Chronic-Treated Rats
2.3. 5-HT2AR Colocalization Studies in the mPFC, DG, NAc, ST, VTA, SNc, and DRN
3. Discussion
4. Materials and Methods
4.1. Animals
4.2. Histological Procedures and Immunocytochemistry
Animals and Fixation
4.3. Immunoperoxidase Experiments
4.4. Double Immunofluorescence Experiments
4.5. Specificity of Antibodies
4.6. Thionin Staining
4.7. Analysis of Sections
4.7.1. Immunoperoxidase Experiments
4.7.2. Double Immunofluorescence Experiments
4.8. Electrophysiological Recordings
4.8.1. Extracellular Single-Unit Recordings
4.8.2. Drugs and Pharmacological Treatments
4.9. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
(±)-DOI | 2,5-dimethoxy-4-iodoamphetamine |
5-HT | 5-hydroxytryptamine |
5-HT2CRs | 5-HT2C receptors |
5-HTARs | 5-HTA receptors |
AN | Acute nicotine |
CN | Chronic nicotine |
DA | Dopamine |
DG | dentate gyrus |
DRN | dorsal raphe nucleus |
GABA | Gamma-aminobutyric acid |
GLU | Glutamate |
HT2A | 5-HTA receptor gene |
IHC | immunohistochemistry |
mPFC | Medial prefrontal cortex |
NAc | nucleus accumbens |
nAChRs | Nicotinic cholinergic receptors |
NN | Naïve nicotine |
PBS | phosphate-buffered saline |
SNc | substantia nigra pars compacta |
ST | Striatum |
TCB-2 | (4-Bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine hydrobromide |
VTA | Ventral tegmental area |
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Lateral Habenula (LHb) | Naïve Nicotine (NN) | Acute Nicotine (AN) | Chronic Nicotine (CN) |
---|---|---|---|
Density 5-HT2AR-IR neurons | 57.1 ± 12.3 | 52.2 ± 13.3 | 51.4 ± 13.9 |
HuC/D-IR neurons | 600 | 608 | 664 |
HuC/D/5-HT2AR-IR | 64 | 56 | 56 |
% of 5-HT2AR-IR | 9.6% (64/664) | 8.4% (56/664) | 7.8% (56/720) |
% area covered by 5-HT2AR-IR | 53.5 ± 8.8 | 67.7 ± 15.8 * | 58.4 ± 11.6 |
Medial Prefrontal Cortex (mPFC) | Naïve Nicotine (NN) | Acute Nicotine (AN) | Chronic Nicotine (CN) |
---|---|---|---|
HuC/D-IR neurons | 242 | 189 | 317 |
HuC/D/5-HT2AR-IR | 454 | 379 | 443 |
% of 5-HT2AR-IR | 65.2% (454/696) | 66.7% (379/568) | 58.3% (443/760) |
% area covered by 5-HT2AR-IR | 75.9 ± 14.1 | 63.3 ± 14.1 * | 76.1 ± 13.4 ^ |
Dentate Gyrus (DG) | NN | AN | CN |
HuC/D-IR neurons | 192 | 138 | 172 |
HuC/D/5-HT2AR-IR | 44 | 99 | 36 |
% of 5-HT2AR-IR | 18.6% (44/236) | 41.8% (99/237) * | 17.3% (36/208) |
% area covered by 5-HT2AR-IR | 57.6 ± 12.9 | 69.6 ± 19.7 | 52.1 ± 15.8 ^ |
Nucleus Accumbens (NAc) | NN | AN | CN |
HuC/D-IR neurons | 33 | 31 | 36 |
HuC/D/5-HT2AR-IR | 59 | 49 | 52 |
% of 5-HT2AR-IR | 64.1% (59/92) | 61.3% (49/80) | 59.1% (52/88) |
% area covered by 5-HT2AR-IR | 27.4 ± 8.9 | 33.6 ± 11.9 | 46.7 ± 25.4 * |
Striatum (ST) | NN | AN | CN |
HuC/D-IR neurons | 298 | 302 | 256 |
HuC/D/5-HT2AR-IR | 302 | 319 | 296 |
% of 5-HT2AR-IR | 50.3% (302/600) | 51.4% (319/621) | 53.6% (296/552) |
% area covered by 5-HT2AR-IR | 71.8 ± 13.5 | 77.9 ± 14.1 | 67.1 ± 12.4 ^ |
Ventral Tegmental Area (VTA) | NN | AN | CN |
HuC/D-IR neurons | 88 | 97 | 104 |
HuC/D/5-HT2AR-IR | 24 | 47 | 32 |
% of 5-HT2AR-IR | 21.4% (24/112) | 32.6% (47/144) | 23.5% (32/136) |
% area covered by 5-HT2AR-IR | 45.4 ± 12.2 | 59.2 ± 14.9 * | 54.3 ± 16.2 |
Substantia Nigra Pars Compacta (SNc) | NN | AN | CN |
HuC/D-IR neurons | 184 | 205 | 232 |
HuC/D/5-HT2AR-IR | 112 | 91 | 108 |
% of 5-HT2AR-IR | 37.8% (112/296) | 30.7% (91/296) | 31.8% (108/340) |
% area covered by 5-HT2AR-IR | 42.8 ± 12.4 | 49.9 ± 13.1 | 49.1 ± 14.5 |
Dorsal raphe Nucleus (DRN) | NN | AN | CN |
HuC/D-IR neurons | 368 | 284 | 264 |
HuC/D/5-HT2AR-IR | 92 | 104 | 132 |
% of 5-HT2AR-IR | 20% (92/460) | 26.8% (104/388) | 33.3% (132/396) |
% area covered by 5-HT2AR-IR | 19.4 ± 5.2 | 20.1 ± 5.9 | 19.1 ± 4.8 |
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Bombardi, C.; Delicata, F.; Tagliavia, C.; Pierucci, M.; Deidda, G.; Casarrubea, M.; De Deurwaerdère, P.; Di Giovanni, G. Acute and Chronic Nicotine Exposures Differentially Affect Central Serotonin 2A Receptor Function: Focus on the Lateral Habenula. Int. J. Mol. Sci. 2020, 21, 1873. https://doi.org/10.3390/ijms21051873
Bombardi C, Delicata F, Tagliavia C, Pierucci M, Deidda G, Casarrubea M, De Deurwaerdère P, Di Giovanni G. Acute and Chronic Nicotine Exposures Differentially Affect Central Serotonin 2A Receptor Function: Focus on the Lateral Habenula. International Journal of Molecular Sciences. 2020; 21(5):1873. https://doi.org/10.3390/ijms21051873
Chicago/Turabian StyleBombardi, Cristiano, Francis Delicata, Claudio Tagliavia, Massimo Pierucci, Gabriele Deidda, Maurizio Casarrubea, Philippe De Deurwaerdère, and Giuseppe Di Giovanni. 2020. "Acute and Chronic Nicotine Exposures Differentially Affect Central Serotonin 2A Receptor Function: Focus on the Lateral Habenula" International Journal of Molecular Sciences 21, no. 5: 1873. https://doi.org/10.3390/ijms21051873