| First Author | Page SJ | Year | 2019 |
| Journal | Am J Physiol Regul Integr Comp Physiol | Volume | 316 |
| Issue | 1 | Pages | R38-R49 |
| PubMed ID | 30354182 | Mgi Jnum | J:269221 |
| Mgi Id | MGI:6272124 | Doi | 10.1152/ajpregu.00344.2017 |
| Citation | Page SJ, et al. (2019) Effects of acute and chronic nicotine on catecholamine neurons of the nucleus of the solitary tract. Am J Physiol Regul Integr Comp Physiol 316(1):R38-R49 |
| abstractText | Nicotine is an addictive drug that has broad effects throughout the brain. One site of action is the nucleus of the solitary tract (NTS), where nicotine initiates a stress response and modulates cardiovascular and gastric function through nicotinic acetylcholine receptors (nAChRs). Catecholamine (CA) neurons in the NTS influence stress and gastric and cardiovascular reflexes, making them potential mediators of nicotine's effects; however nicotine's effect on these neurons is unknown. Here, we determined nicotine's actions on NTS-CA neurons by use of patch-clamp techniques in brain slices from transgenic mice expressing enhanced green fluorescent protein driven by the tyrosine hydroxylase promoter (TH-EGFP). Picospritzing nicotine both induced a direct inward current and increased the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in NTS-CA neurons, effects blocked by nonselective nAChR antagonists TMPH and MLA. The increase in sEPSC frequency was mimicked by nAChRalpha7 agonist AR-R17779 and blocked by nAChRalpha7 antagonist MG624. AR-R17779 also increased the firing of TH-EGFP neurons, an effect dependent on glutamate inputs, as it was blocked by the glutamate antagonist NBQX. In contrast, the nicotine-induced current was mimicked by nAChRalpha4beta2 agonist RJR2403 and blocked by nAChRalpha4beta2 antagonist DHbetaE. RJR2403 also increased the firing rate of TH-EGFP neurons independently of glutamate. Finally, both somatodendritic and sEPSC nicotine responses from NTS-CA neurons were larger in nicotine-dependent mice that had under gone spontaneous nicotine withdrawal. These results demonstrate that 1) nicotine activates NTS-CA neurons both directly, by inducing a direct current, and indirectly, by increasing glutamate inputs, and 2) NTS-CA nicotine responsiveness is altered during nicotine withdrawal. |
